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A randomized study of metabolic effects of four oral contraceptive preparations containing levonorgestrel plus ethinyloestradiol in different regimens

  • Chapter
The Development of a New Triphasic Oral Contraceptive

Abstract

Healthy, normotensive, well-motivated, young women were assigned at random to one of four oral contraceptives containing levonorgestrel plus ethinyloestradiol (21-day cyclic treatments) and 80 completed six treatment cycles. Metabolic and endocrine status tests were conducted in the pretreatment cycle and at intervals during the study. All four products appeared to be equally efficient inhibitors of ovulation, as judged by plasma hormone indices. Deterioration of oral glucose tolerance and insulin responses were noted with all preparations, except a triphasic formulation. All products increased the concentration of triglycerides in fasting plasma, though the extent of the increase appeared to be dose-related. Only the highest dose product significantly increased plasma cholesterol. Cholesterol in high-density lipoproteins was significantly increased by an oestrogenic biphasic product, but significantly decreased by a high-dose fixed combination. Significant increases in fibrinogen, plasminogen, and coagulation factors VII, VIII and X were observed, especially with the highest dose product and the oestrogen-dominated biphasic. Antithrombin III was suppressed. Renin activity and renin-substrate concentration were elevated, while plasma renin concentration was reduced: again the effects appeared to be related to the oestrogen dose.

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References

  1. Briggs, M. H. (1977a). Combined oral contraceptives. In Regulation of Human Fertility, pp. 253–282. ( Copenhagen: Scriptor )

    Google Scholar 

  2. Hawkins, D. F. and Elder, M. G. (1979). Human Fertility Control, pp. 49–91. ( London: Butterworths )

    Google Scholar 

  3. Berel, V. and Kay, C. R.;1977). Mortality among oral contraceptive users. Lancet, 2, 727

    Google Scholar 

  4. Vessey, M. P., McPherson, K. and Johnson, B. (1977). Mortality among women participating in the Oxford/Family Planning Association ContraceptiveStudy. Lancet, 2, 731

    Article  CAS  PubMed  Google Scholar 

  5. Royal College of General Practitioners (1974). Oral Contraceptives and Health, pp. 10–11. ( London: Pitman )

    Google Scholar 

  6. Belsey, M. A., Russell, Y. and Kinnear, K. 1979 ). Cardiovascular disease and oral contraceptives: a reappraisal of vital statistics data. Fam. Plain. Perspect., 11, 84

    Article  CAS  Google Scholar 

  7. Tieze, C. (1979). The pill and mortality from cardiovascular disease: another look. Fam. Plann. Perspect., 11, 80

    Article  Google Scholar 

  8. Briggs, M. H. (1979a). Recent biological studies in relation to low dose hormonal contraceptives. Br. J. Fam. Plann., 5, 25

    Google Scholar 

  9. Goldzieher, J. W., De La Pena, A., Chenault, C. B. and Cervantes, A. (1975). Comparative studies of the ethynyl estrogens used in oral contraceptives. Am..J. Obstet. Gynecol., 122, 615–619

    CAS  PubMed  Google Scholar 

  10. Briggs, M. H. (1977b). The beagle dog and contraceptive steroids. Life Sci., 21, 275

    Article  CAS  PubMed  Google Scholar 

  11. Fortherby, ‘K. and James, F. (1972). Metabolism of synthetic steroids. Ada. Ster. Biochem. Pharmacol., 3, 67

    Google Scholar 

  12. Jones, R. C., Singer, A. C. and Edgren, R. A. (1979). The biological activities of norgestrel and its enantiomers. Int. J. Fenil., 24, 39

    CAS  Google Scholar 

  13. Sisenwine, S. F., Liu, A. L., Kimmel, H. B. and Ruelius, H. W. (1977). Conversion of d-norgestrel-3-oxime-17-acetate to d-norgestrel in female rhesus monkeys. Contraception, 15, 27

    Article  Google Scholar 

  14. Viinikka, L., Ylikorkala, O., Vihko, B., Wijnaad, H. P. and Booij, M. (1979). Metabolism of a new synthetic progestogen, ORG 2969, in female volunteers. Eur. f. Clin. Pharmacol., 15, 349

    Article  CAS  Google Scholar 

  15. Briggs, M. H. and Briggs, M. (1976). Molecular biology and oral contraception. N.Z. Med.J., 83, 257

    CAS  PubMed  Google Scholar 

  16. Briggs, M. H. (1979b). Biochemical basis for the selection of oral contraceptives. Int. J. Gynaecol. Obstet., 16, 509

    CAS  Google Scholar 

  17. Briggs, M. H. and Briggs, M. (1980). Relative contraindications to oral contraceptives and their use in adolescence, puerperium, and menopause. Proceedings of the 4th International Meeting on Fertility Control, Genoa, in press. (Palermo: Cofese Edizioni)

    Google Scholar 

  18. Johansson, E. D. B. (1970). Simplified procedure for the assay of progesterone. Acta Endocrinol. Suppl., 147, 188

    CAS  Google Scholar 

  19. Edqvist, L. E. and Johansson, E. D. B. (1972). Radioimmunoassay of oestrone and oestradiol in human and bovine peripheral plasma. Acta Endocrinol., 71, 716

    CAS  PubMed  Google Scholar 

  20. Karonen, S. L., Lähteenmäki, P., Hohenthal, U., Aldercreutz, H. (1978). Evaluation of the double antibody—solid phase radioimmunoassay technique in plasma LH and FSH. Scand.]. Clin. Invest., 38, 1

    Google Scholar 

  21. Cramp, D. G. (1967). New automated enzymatic method for measuring glucose by glucose oxidase. J. Clin. Pathol., 20, 910

    Article  CAS  PubMed  Google Scholar 

  22. Herbert, V., Lau, K., Gottleib, C. W., Bleicher, S. J. (1965). Coated charcoal immunoassay of insulin. J. Clin. Endocrinol.Metab., 25, 1375

    Article  CAS  PubMed  Google Scholar 

  23. Clauss, A. (1957). Gerinnungsphysiologische Schnellmethode zur Bastimmuny des Fibrinogens. Acta Haematol., 17, 237

    Article  CAS  PubMed  Google Scholar 

  24. Poller, L., Thomson, J. M., Sear, C. H. J., Thomas, W. (1971). Identification of a congenital defect of factor VII in a colony of beagle dogs: clinical use of the plasma. J. Clin. Pathol., 24, 626

    Article  CAS  PubMed  Google Scholar 

  25. Breckenridge, R. T. and Ratnoff, O. D. (1962). Studies on the nature of the circulating anticoagulant directed against antihacmophilic factors. Blood, 20, 137

    CAS  PubMed  Google Scholar 

  26. Aurell, L., Simonsson, R., Aridly, S., Karlsson, G., Friberger, P., Claesan, G. (1978). Chromogenic peptide substrates for factor Xa. Haemostasis, 7, 92

    CAS  PubMed  Google Scholar 

  27. Abllgaard, U., Lie, M., Odegard, O. R. (1976). Antithrombin assay with new chromogenic substrates (S-2238 and Chromozym TH). Thromb. Res., 11, 549

    Article  Google Scholar 

  28. Soria, J., Soria, C., Samama, M. (1975). Measurement of plasminogen using chromogenic tripeptide. Organization des Laboratorires-Biologie Prospective IH Collegue de point-a-moussan. L/Expansion Scientifique Française

    Google Scholar 

  29. Delorme, A., Guyene, P. T., Corvol, P., Menard, J. (1976). Methodologie problems in plasma renin activity measurements. Am. J. Med., 61, 725

    Article  CAS  PubMed  Google Scholar 

  30. Campillo, J. E., Del Rio, C. G., Quesada, T., Osorio, C. (1976). Simultaneous measurement of renin and renin substrate concentration in human plasma by a simple kinetic method. Clin. Chim. Acta, 73, 475

    Article  CAS  PubMed  Google Scholar 

  31. Robertson, G. and Cramp, D. G. (1970). Evaluation of cholesterol determination in serum and serum lipoprotein fractions by semi-automated fluorimetric method. J. Clin. Pathol., 23, 243

    Article  CAS  PubMed  Google Scholar 

  32. Cramp, D. G. and Robertson, G. (1968). Fluorimetric assay of tri-glycerides by a semi-automated method. Anal. Biochem., 25, 246

    Article  CAS  PubMed  Google Scholar 

  33. Burstein, M. and Samaille, J. (1960). Rapid method for cholesterol in serum a and ß lipoproteins. Clin. Chim. Acta, 5, 609

    Article  CAS  PubMed  Google Scholar 

  34. Briggs, M. H., Pitchford, A. G., Staniford, M., Barker, H. M. and Taylor, D. (1970). Metabolic effects of steroid contraceptives. Adv. Steroid Biochem. Pharmacol., 2, 1 11

    Google Scholar 

  35. Briggs, M. (1975). Biochemical effects of oral contraceptives. Adv. Steroid Biochem. Pharmacol., 5, 65

    Google Scholar 

  36. F’otherby, K. (1977). Low doses of gestagens as fertility regulating agents. In Diczfalusy, E. (ed.) Regulation of Human Fertility, pp. 283 322. Copenhagen: Scriptor

    Google Scholar 

  37. Briggs, M. and Briggs, M. H. (1977). Low dose oral contraceptives. OB/CYN Digest, February, 12–16

    Google Scholar 

  38. Rozenbaum, H. (1978). Low dose estrogen/progestogen combinations. Rév. Méd. (Paris), 19, 1821

    Google Scholar 

  39. Korba, V. D. and Heil, C. G. (1975). Eight years of fertility control with norgestrel-ethinyl estradiol: an updated clinical review. Fertil. Steril., 26, 973

    CAS  PubMed  Google Scholar 

  40. Larranaga, A., Sartoretto, J. N., Winterhalter, M., Filho, F. N. (1978). Clinical evaluation of two biphasic and one triphasic norgestrel/ethinyl estradiol regimens. Int. 7. Fertil., 23, 193

    CAS  Google Scholar 

  41. Briggs, M. H. and Briggs (1977). Clinical and biochemical investigations of a variable-dose combined type oral contraceptive. Curr. Med. Res. Opin., 5, 212

    Article  Google Scholar 

  42. Zador, G. (1979). Fertility regulation using triphasic administration of ethinyl oestradiol and levonorgestrel in comparison with the 30 plus 150µg fixed dose regime. Acta Obstet. Gynecol. Scand., Suppl., 88, 43

    Article  CAS  Google Scholar 

  43. Lachnit-Fixson, U. (1979). The first three-stage preparation for hormonal contraception. Clinical results. Mauch. Med. Irochenschr., 121, 1421

    CAS  Google Scholar 

  44. Woutersz, T. B. (1975). Profile of a new low dose combination estrogen and progestogen oral contraceptive: a review of nine clinical studies. J. Reprod. Med., 15, 87

    CAS  PubMed  Google Scholar 

  45. Woutersz, T. B. (1976). Three and one-half years’ experience with a lower-dose combination oral contraceptive. J. Reprod. Med., 16, 338

    CAS  PubMed  Google Scholar 

  46. Briggs, M. H. and Briggs, M. (1976). Clinical and biochemical investigations of an ultra low-dose combined type oral contraceptive. Curr. Med. Res. Opin., 3, 618

    Article  CAS  Google Scholar 

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Authors
  1. M. Briggs
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  2. M. Briggs
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Editors and Affiliations

  1. Endocrinology, Medical College of Georgia, 30912, Augusta, Georgia, USA

    R. B. Greenblatt (Professor Emeritus) (Professor Emeritus)

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Briggs, M., Briggs, M. (1980). A randomized study of metabolic effects of four oral contraceptive preparations containing levonorgestrel plus ethinyloestradiol in different regimens. In: Cortés-Prieto, J., Campos-da-Paz, A., Greenblatt, R.B. (eds) The Development of a New Triphasic Oral Contraceptive. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-6666-9_6

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  • DOI: https://doi.org/10.1007/978-94-011-6666-9_6

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-011-6668-3

  • Online ISBN: 978-94-011-6666-9

  • eBook Packages: Springer Book Archive

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