• Thomas Rabe
  • Ludwig Kiesel
  • Benno Runnebaum
Part of the Current Topics in Neuroendocrinology book series (CT NEUROENDOCRI, volume 5)


The most efficient methods of female contraception inhibit ovulation by disturbing the endogenous endocrine-regulating mechanisms, The ovulation inhibitors in current use depend on a constant level of active synthetic hormonal steroids during the menstrual cycle. This constant hormonal steroid concentration in the serum is achieved either by daily intake or by the use of long-acting depot injections. These methods combine a high efficiency with a relatively low percentage of side-effects. However, they almost always impair the cyclic physiology, thus giving rise to fears of long-term side-effects. Another disadvantage is that an almost continous intake of hormones is necessary, whereby significant quantities of hormones are ingested, although the use of new hormonal stereoids may slightly decrease the side-effects. Safety might be increased if the pharmacological inhibition of the menstrual cycle were reduced to a period of 1 or 2 days.


Progesterone Receptor Luteal Phase Corpus Luteum Vaginal Ring Progesterone Secretion 
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.



human chorionic gonadotropin


gonadotropin-releasing hormone


luteinizing hormone


adrenocorticotropin-releasing hormone


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Aitken RJ, Harper MJK (1977) New methods for the regulation of implantation. Contraception 16:227–241PubMedCrossRefGoogle Scholar
  2. Anderson J, Clark JH, Peck EJ (1972) Oestrogen and nuclear binding sites: determination of specific sites by 3H-oestradiol exchanges. Biochem J 126:561–567PubMedGoogle Scholar
  3. Atger M, Baulieu E-E, Milgrom E (1974) An investigation of progesterone receptors in guinea pig vagina, uteine cervix, mammary glands, pituitary and hypothalamus. Endocrinology 94:161–167PubMedCrossRefGoogle Scholar
  4. Azadian-Boulanger G, Secchi J, Laraque F, Raynaud JP, Sakiz E (1976) Action of a mid-cycle contraceptive (R 2323) on the human endometrium. Am J Obstet Gynecol 125:1049–1056PubMedGoogle Scholar
  5. Bacic M, Wesselius de Casparis A, Diczfalusy E (1970) Failure of large doses of ethinyl estradiol to interfere with early embryonic development in the human species. Am J Obstet Gynecol 107:531–534PubMedGoogle Scholar
  6. Bahl OP (1969) Human chorionic gonadotrophin II. Nature of the carbohydrate units. J Biol Chem 244:575–583PubMedGoogle Scholar
  7. Banik UD, Pincus G (1962) Effect of steroidal antiprogestins on implantation of fertilized eggs of rats and mice. Proc Soc Exp Biol Med 111:595–602PubMedGoogle Scholar
  8. Baulieu E-E, Alberga A, Jung I, Lebeau M-C, Mercier-Bodard C, Milgrom E, Raynaud J-P, Raynaud-Jammet C, Rochefort H, Truong H, Röbel P (1971) Metabolism and protein binding of sex steroids in target organs: an approach to the mechanism of hormone action. Recent Prog Hormone Res 27:351Google Scholar
  9. Bayard F, Damilano S, Röbel P, Baulieu E-E (1975) Récepteurs de l’oestradiol et de la progestérone dans l’endomètre humain au cours du cycle menstruel. C R Séances Acad Sci 281:1341–1344Google Scholar
  10. Beyer G, Zeilmarker GH (1974) Prolonged pseudo-pregnancy in mice bearing ectopic trophoblastic tissue. J Endocrinol 61:509–510PubMedCrossRefGoogle Scholar
  11. Beyer B, Terenius L, Brueggemeier RW, Ranade W, Counsell RE (1976) Synthesis of potential antiprogestins. Steroids 27:123–131CrossRefGoogle Scholar
  12. Bouin P, Ancel P (1910) Sur les fonctions du corps jaune gestatif. I. Sur le déterminisme de la préparation de l’utérus à la fixation de l’oeuf. J Physiol Pathol Gen 12:1–16Google Scholar
  13. Brown WE, Bradbury JT (1947) A study of the physiologic action of human chorionic hormone. Am J Obstet Gynecol 53:749–757PubMedGoogle Scholar
  14. Butenandt A, Westphal U, Hohlweg W (1934) Über das Hormon des Corpus lutenum. Hoppe-Zeylers Z Physiol 227:84–98CrossRefGoogle Scholar
  15. Chamboon Y (1949) Besoins endocriniens qualitatifs et quantitatifs de l’ovoimplantation chez la lapine. C R Soc Biol (Paris) 143:1172–1175Google Scholar
  16. Channing CP, Sakai C, Bahl OP (1976) Role of the carbohydrate residues of human chorionic gonadotropin (hCG) on its ability to bind and stimulate cyclic AMP accumulation in porcinegranulosa cells. Fed Proc 35:798Google Scholar
  17. Channing CP, Sakai C, Bahl OP (1977) Role of carbohydrate residues of human chorionic gonadotropin in binding and stimulation of cyclic AMP and progesterone secretion by porcine granulosa cells. Endocrinology 103:341–348CrossRefGoogle Scholar
  18. Channing CP, Engel B, Bahl OP (1978) Role of carbohydrate residues of human chorionic gonadotropin in stimulation of luteinization of monkey granulosa cell cultures. Biol Reprod 18:707PubMedCrossRefGoogle Scholar
  19. Clark SW, Sweet F, Warren JC (1974) Interceptive activity of 16a-Bromoacetoxyprogesterone. Biol Reprod 11:519–528PubMedCrossRefGoogle Scholar
  20. Clark SW, Sweet F, Warren JC (1975) Synthesis and use of affinity-labeling steroids for interceptive purposes. Am J Obstet Gynecol 121:864PubMedGoogle Scholar
  21. Courrier R (1945) Cited in: Reynolds SRM, Hoeber PH (eds) Physiology of the uterus. Harper New York (1949) p111Google Scholar
  22. Csapo AI (1976) Prostaglandin impact. In: Samuelsson B, Paoletti R (eds) Advances in prostaglandin and thromboxane research, vol 2. Raven, New York, pp 705–718Google Scholar
  23. Csapo AI, Pulkkinen MP (1973) The effect of estradiol replacement therapy on early pregnant luteectomized patients. Am J Obstet Gynecol 117:987–990PubMedGoogle Scholar
  24. Csapo AI, Pulkkinen M (1978) Indispensability of human corpus luteum in the maintenance of early pregnancy luteectomy evidence. Obstet Gynecol Survey 83:69–81CrossRefGoogle Scholar
  25. Csapo AI, Pulkkinen MP, Kaihola HL (1974) The relationship between timing of luteectomy and the incidence of complete abortions. Am J Obstet Gynecol 118:985–989PubMedGoogle Scholar
  26. Deanesly R (1960) Implantation and early pregnancy in ovariectomized guineapigs. J Reprod Fertil 1:242CrossRefGoogle Scholar
  27. Feder HH, Resko JA, Goy RW (1968) Progesterone concentrations in the arterial plasma of guinea-pigs during the oestrous cycle. J Endocrinol 40:505PubMedCrossRefGoogle Scholar
  28. Fraenkel S (1910) Die Funktion des Corpus luteum. Arch Gynäkol 68:438CrossRefGoogle Scholar
  29. Fried PH, Rakoff AE (1952) The effects of chorionic gonadotropin and prolactin on the maintenance of corpus luteum function. Eur J Clin Endocrinol Metabol 12:321–327CrossRefGoogle Scholar
  30. Fuchs AR, Beling CG (1974) Evidence of early ovarian recognition of blastocysts in rabbits. Endocrinology 95:1054–1058PubMedCrossRefGoogle Scholar
  31. Gase JM, Renoir JM, Radanyi CH, Joab I, Tuohima P, Baulieu EE (1984) Progesterone receptor in the chick oviduct: an immunohistochemical study with antibodies to distinct receptor components. J Cell Biol (in press)Google Scholar
  32. Good RG, Moyer DL (1968) Estrogen-progesterone relationships in the development of secretory endometrium. Fertil Steril 19:37–49PubMedGoogle Scholar
  33. Guériguian JL, Sawyer ME, Pearlman WH (1974) A comparative study of progesterone-and cortisol-binding activity in the uterus and serum of pregnant and non-pregnant women. J Endocrinol 61:331–345PubMedCrossRefGoogle Scholar
  34. Hanson FW, Powell JE, Stevens VC (1971) Effects of hCG and human pituitary LH on steroid secretion and functional life span of the human corpus luteum. J Clin Endocrinol Metabol 32:211–215CrossRefGoogle Scholar
  35. Haour F (1976) Rat chorionic gonadotropin (rCG): radioreceptor assay and correlation with corpus luteum function during gestation. In: V International Congress of Endocrinology Excerpta Medica Int Congr Series, Amsterdam (Abstract 777), p 321Google Scholar
  36. Haukkamaa M, Karjalainen O, Luukkainen T (1971) In vitro binding of progesterone by the human endometrium during the menstrual cycle and by hyperplastic, atrophic, and carcinomatous endometrium. Am J Obstet Gynecol 111:205PubMedGoogle Scholar
  37. Henzl MR, Segre EJ, Nakamura RM (1973) The influence of oxymetholone on the HCG-stimulated corpus luteum. Contraception 8:515–520CrossRefGoogle Scholar
  38. Herrmann W, Wyss R, Riondel A, Philibert D, Teutsch G, Sakiz E, Baulieu E-E (1982) Effect of an antiprogesterone in women: interruption of the menstrual cycle and of early pregnancy. C R Séances Acad Sci 294:933–938Google Scholar
  39. Jaffe RB, Lee PA, Midgley AR (1969) Serum gonadotropins before, at the inceptions of, and following human pregnancy. J Clin Endocrinol Metab 29:1281–1283PubMedCrossRefGoogle Scholar
  40. Jänne O, Kontula K, Luukkainen T, Vihko R (1975) Oestrogen-induced progsterone in human uterus. J Steroid Biochem 6:501–509PubMedCrossRefGoogle Scholar
  41. Johannson DB (1971) Depression of the progesterone levels in women treated with synthetic gestagens after ovulation. Acta Endocrinol (Copenh) 68:779Google Scholar
  42. Kendle KE (1979) Current investigations of antiprogestational steroids. In: Agrawal MK (ed) Antihormones. Elsevier/North Holland Biomedical Press Amsterdam, pp 293–305Google Scholar
  43. Knobil E (1973) On the regulation of the primate corpus luteum. Biol Reprod 8:246–258Google Scholar
  44. Kontula K (1975a) Cytosol progesterone receptor in mammalian uterus. Academic Dissertation, University of Helsinki, FinlandGoogle Scholar
  45. Kontula K (1975b) Progesterone-binding proteins from endometrium and myometrium of sheep uterus: a comparative study. Acta Endocrinol (Copenh) 78:593–603Google Scholar
  46. Kontula K (1975c) Progesterone binding protein in human myometrium binding site concentration in relation to endogenous progesterone and estradiol-17β levels. J Steroid Biochem 6:1555–1561PubMedCrossRefGoogle Scholar
  47. Kontula K, Jänne O, Luukkainen T, Vihko R (1973) Progesterone-binding protein in human myometrium. Ligand specificity and some physicochemical characteristics. Biochem Biophys Acta 328:145–153Google Scholar
  48. Kontula K, Jänne O, Luukkainen R, Vihko R (1974a) Progesterone-binding protein in human myometrium. Influence of metal ions on binding. J Clin Endocrinol Metabol 38:500–503CrossRefGoogle Scholar
  49. Kontula K, Jänne O, Rajakoski E, Tanhuanpää E, Vihko R (1974b) Ligand specificity of progesterone-binding proteins in guinea pig and sheep. J Steroid Biochem 5:39–44PubMedCrossRefGoogle Scholar
  50. Kontula K, Jänne O, Vihko R, Jager E, Visser J, Zeelen F (1975) Progesterone-binding proteins: in vitro binding and biological activity of different steroidal ligands. Acta Endocrinol (Copenh) 78:574–592Google Scholar
  51. Leavitt WW, Toft DO, Strott CA, O’Malley BW (1974) A specific progesterone receptor in the hamster uterus: physiologic properties and regulation during the estrous cycle. Endocrinology 94:1041–1053PubMedCrossRefGoogle Scholar
  52. Luu Thi MT, Baulieu E-E, Milgrom E (1975) Comparison of the characteristics and of the hormonal control of endometrial and myometrial progesterone receptors. J Endocrinol 66:349–356CrossRefGoogle Scholar
  53. McGuire JL, De Delia C (1971) In vitro evidence for a progestogen receptor in the rat and rabbit uterus. Endocrinology 88:1099–1103PubMedCrossRefGoogle Scholar
  54. Meyer RK (1972) Chorionic gonadotropin, corpus luteum function and embryo implantation in the rhesus monkey. In: Dicfalusy E, Standley CC (eds) The use of non-human primates in research on human reproduction. WHO, Genf, pp 214–217Google Scholar
  55. Milgrom E, Baulieu E-E (1970a) Progesterone in uterus and plasma. I. Binding in ratuterus 105,000 g supernatant. Endocrinology 87:276–287PubMedCrossRefGoogle Scholar
  56. Milgrom E, Baulieu E-E (1970b) Progesterone in the uterus and the plasma. II. The role of hormone availability and metabolism on selective binding to uterus protein. Biochem Biophys Res Commun 40:723–730PubMedCrossRefGoogle Scholar
  57. Milgrom E, Atger M, Baulieu E-E (1970) Progesterone in uterus and plasma. IV. Progesterone receptor(s) in guinea pig uterus cytosol. Steroids 16:741–754PubMedCrossRefGoogle Scholar
  58. Milgrom E, Perrot M, Atger M, Baulieu E-E (1972a) Progesterone in uterus and plasma. V. An assay of the progesterone Cytosol receptor of the guinea pig uterus. Endocrinology 90:1064–1070PubMedCrossRefGoogle Scholar
  59. Milgrom E, Atger M, Perrot M, Baulieu E-E (1972b) Progesterone in uterus and plasma. Uterine progesterone receptors during the estrus cycle and implantation in the guinea pig. Endocrinology 90:1071–1078PubMedCrossRefGoogle Scholar
  60. Milgrom E, Luu Thi M, Atger M, Baulieu E-E (1973a) Mechanism regulating the concentration and the conformation of progesterone receptor(s) in the uterus. J Biol Chem 248:6366–6374PubMedGoogle Scholar
  61. Milgrom E, Luu Thi MT, Baulieu E-E (1973b) Control mechanisms of steroid hormone receptors in the reproductive tract. Acta Endocrinol (Copenh) [Suppl] 180:380–403Google Scholar
  62. Neill JD, Johansson EDB, Knobil E (1969) Failure of hysterectomy to influence the normal pattern of cyclic progesterone secretion in the rhesus monkey. Endocrinology 84:464–465PubMedCrossRefGoogle Scholar
  63. Neumann F, Elger W (1971) Kritische Überlegungen zu den biologischen Grundlagen von Toxizitätsstudien mit Seroid-(Sexual-)hormonen. In: Plötz EJ, Haller J (eds) Methodik der Steroidtoxikologie. Georg Thieme, Stuttgart, pp 6–48Google Scholar
  64. Niswender GD, Menon KMJ, Jaffe RB (1972) Regulation of the corpus luteum during the menstrual cycle and early pregnancy. Fertil Steril 23:432–442PubMedGoogle Scholar
  65. Oriol-Bosch A, Cortes J (1975) Effects of postovulatory estradiol benzoate administration on womens’ ovarian function. Fertil Steril 26:405–412PubMedGoogle Scholar
  66. Philibert D, Raynaud JP (1974) Binding of progesterone and R 5020, a highly potent progestin, to human endometrium and myometrium. Contraception 10:457–466PubMedCrossRefGoogle Scholar
  67. Philibert D, Dereadt R, Teutsch G (1981) 8th International Congress of Pharmacology, Tokyo, Congress Proceedings, Abstract No. 1463, p g668Google Scholar
  68. Rao BR, Wiest WG, Allen WM (1973) Progesterone “receptor” in rabbit uterus. I. Characterization and estradiol-17ß augmentation. Endocrinology 92:1229–1240PubMedCrossRefGoogle Scholar
  69. Raynaud JP, Bonne C, Bouton MM, Moguilewsky M, Philibert D, Azadian-Boulanger G (1975) Screening for anti-hormones by receptor studies. J Steroid Biochem 6:615–622PubMedCrossRefGoogle Scholar
  70. Raynaud JR, Ojasoo T, Labrie F (1981) Steroid hormones-agonists and antagonists. In: Lewis GP, Ginsburg M (eds) Mechanism of steroid action. Macmillan, London, pp 145–158Google Scholar
  71. Reel JR, Humphrey RR, Shih Y, Windsor B, Sakowski R, Greger PL, Edgren R (1979) Competitive progesterone antagonists: receptor binding and biologic activity of testosterone and 19-nortestosterone derivates. Fertil Steril 31:553Google Scholar
  72. Reinius S, Fritz GR, Knobil E (1973) Ultrastructure and endrocrinological correlation of an early implantation site in the rhesus monkey. J Reprod Fertil 32:171–173PubMedCrossRefGoogle Scholar
  73. Ross GT, Cargille GM, Lipsett MB, Rayford PL, Marshall JR, Strott CA, Rodbard D (1970) Pituitary and gonaldal hormones in women during spontaneous and induced ovulatory cycles. Recent Prog Hormone Res 26:1Google Scholar
  74. Sakai CN, Engel B, Channing CP (1977) Ability of extract of pig corpus luteum to inhibit binding of 125I-labelled human chorionic gonadotropin in porcine granulosa cells. Proc Soc Exp Biol 155:373–376PubMedGoogle Scholar
  75. Sakiz E, Azadian-Boulanger G (1971) R 2323-an original contraceptive compound. In: James VHT, Martini L (eds) Proc IIIrd Int Congr Hormonal Steroids, Hamburg 1970. Excerpta Medica Int Congr Series 219:865–871Google Scholar
  76. Sakiz E, Azadian-Boulanger G, Raynaud JP (1972) Antiestrogens, antiprogesterones. In: Proceedings of the Fourth International Congress of Endocrinology, Washington. Excerpta Medica, Int Congr Series, Amsterdam, 18–24 June 1972, pp 988–994Google Scholar
  77. Sakiz E, Azadian-Boulanger G, Larraque F, Raynaud JP (1974) A new approach to es-trogen-free contraception based on progesterone receptor blockade by mid-cycle administration of ethyl norgestrienone (R 2323). Contraception 10:467–480PubMedCrossRefGoogle Scholar
  78. Sakiz E, Azadian-Boulanger G, Ojasoo T, Laraque F (1976) Contraceptive efficacy of one-weekly oral administration of 2,5 mg R 2323. Contraception 14:275–284PubMedCrossRefGoogle Scholar
  79. Saxena BB, Hasan SH, Haour F, Schmidt-Gollwitzer M (1974) Radioreceptor assay of human chorionic gonadotropin: detection of early pregnancy. Science 184:793–795PubMedCrossRefGoogle Scholar
  80. Short RY (1969) Implantation and the maternal recognition of pregnancy. In: Wolstenholme GEW, O’Connor M (eds) Ciba Symposium on Foetal Autonomy. Churchill, London, pp 2–31CrossRefGoogle Scholar
  81. Short RV (1972) Role of hormones in sex cycles. In: Austin CR, Short RV (eds) Reproduction in mammals, vol 3. University Press, Cambridge, p 42Google Scholar
  82. Smith RG, Iramain CA, Buttram VC, O’Malley BW (1975) Purification of human uterine progesterone receptor. Nature 253:271–272PubMedCrossRefGoogle Scholar
  83. Thomas PJ (1973) Steroid hormones and their receptors. J Endocrinol 57:333–359PubMedCrossRefGoogle Scholar
  84. Trams G, Brewitt H, Möllmann G, Maas H (1973) Effect of progesterone on RNA and protein synthesis in the rat uterus. Acta Endocrinol (Copenh) 73:740–750Google Scholar
  85. Van de Wiele RL, Bogumil J, Dyrenfurth I, Ferin M, Jewelewicz R, Warren M, Rizkallah T, Mikhail G (1970) Mechanisms regulating the menstrual cycle in women. Recent Prog Hormone Res 26:63Google Scholar
  86. Viinikka L, Victor A, Jänne O, Raynaud J-P (1975) The plasma concentration of a synthetic progestin, R 2323, released from poly silastic vaginal rings. Contraception 12:309–316PubMedCrossRefGoogle Scholar
  87. Warren JC (1973) Progesterone: implications for fertility control. Biol Reprod 8:259Google Scholar
  88. Wiest WG, Rao BR (1971) Progesterone binding proteins in rabbit uterus and human endometrium. Schering Workshop on steroid hormone “receptors”, Berlin 7–9 December 1970. In: Raspe G (ed) Advances in the biosciences, vol 7. Pergamon, Oxford, p 251Google Scholar

Copyright information

© Spriger-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • Thomas Rabe
  • Ludwig Kiesel
  • Benno Runnebaum
    • 1
  1. 1.Department of Gynecological EndocrinologyUniversity Hospital for WomanHeidelbergFederal Republic of Germany

Personalised recommendations