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

  • M. Briggs
  • M. Briggs


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.


Luteinizing Hormone Oral Contraceptive Renin Activity Oral Contraceptive User Plasma Renin Concentration 
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  1. 1.
    Briggs, M. H. (1977a). Combined oral contraceptives. In Regulation of Human Fertility, pp. 253–282. ( Copenhagen: Scriptor )Google Scholar
  2. 2.
    Hawkins, D. F. and Elder, M. G. (1979). Human Fertility Control, pp. 49–91. ( London: Butterworths )Google Scholar
  3. 3.
    Berel, V. and Kay, C. R.;1977). Mortality among oral contraceptive users. Lancet, 2, 727Google Scholar
  4. 4.
    Vessey, M. P., McPherson, K. and Johnson, B. (1977). Mortality among women participating in the Oxford/Family Planning Association ContraceptiveStudy. Lancet, 2, 731CrossRefPubMedGoogle Scholar
  5. 5.
    Royal College of General Practitioners (1974). Oral Contraceptives and Health, pp. 10–11. ( London: Pitman )Google Scholar
  6. 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, 84CrossRefGoogle Scholar
  7. 7.
    Tieze, C. (1979). The pill and mortality from cardiovascular disease: another look. Fam. Plann. Perspect., 11, 80CrossRefGoogle Scholar
  8. 8.
    Briggs, M. H. (1979a). Recent biological studies in relation to low dose hormonal contraceptives. Br. J. Fam. Plann., 5, 25Google Scholar
  9. 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, 615–619PubMedGoogle Scholar
  10. 10.
    Briggs, M. H. (1977b). The beagle dog and contraceptive steroids. Life Sci., 21, 275CrossRefPubMedGoogle Scholar
  11. 11.
    Fortherby, ‘K. and James, F. (1972). Metabolism of synthetic steroids. Ada. Ster. Biochem. Pharmacol., 3, 67Google Scholar
  12. 12.
    Jones, R. C., Singer, A. C. and Edgren, R. A. (1979). The biological activities of norgestrel and its enantiomers. Int. J. Fenil., 24, 39Google Scholar
  13. 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, 27CrossRefGoogle Scholar
  14. 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, 349CrossRefGoogle Scholar
  15. 15.
    Briggs, M. H. and Briggs, M. (1976). Molecular biology and oral contraception. N.Z. Med.J., 83, 257PubMedGoogle Scholar
  16. 16.
    Briggs, M. H. (1979b). Biochemical basis for the selection of oral contraceptives. Int. J. Gynaecol. Obstet., 16, 509Google Scholar
  17. 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. 18.
    Johansson, E. D. B. (1970). Simplified procedure for the assay of progesterone. Acta Endocrinol. Suppl., 147, 188Google Scholar
  19. 19.
    Edqvist, L. E. and Johansson, E. D. B. (1972). Radioimmunoassay of oestrone and oestradiol in human and bovine peripheral plasma. Acta Endocrinol., 71, 716PubMedGoogle Scholar
  20. 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, 1Google Scholar
  21. 21.
    Cramp, D. G. (1967). New automated enzymatic method for measuring glucose by glucose oxidase. J. Clin. Pathol., 20, 910CrossRefPubMedGoogle Scholar
  22. 22.
    Herbert, V., Lau, K., Gottleib, C. W., Bleicher, S. J. (1965). Coated charcoal immunoassay of insulin. J. Clin. Endocrinol.Metab., 25, 1375CrossRefPubMedGoogle Scholar
  23. 23.
    Clauss, A. (1957). Gerinnungsphysiologische Schnellmethode zur Bastimmuny des Fibrinogens. Acta Haematol., 17, 237CrossRefPubMedGoogle Scholar
  24. 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, 626CrossRefPubMedGoogle Scholar
  25. 25.
    Breckenridge, R. T. and Ratnoff, O. D. (1962). Studies on the nature of the circulating anticoagulant directed against antihacmophilic factors. Blood, 20, 137PubMedGoogle Scholar
  26. 26.
    Aurell, L., Simonsson, R., Aridly, S., Karlsson, G., Friberger, P., Claesan, G. (1978). Chromogenic peptide substrates for factor Xa. Haemostasis, 7, 92PubMedGoogle Scholar
  27. 27.
    Abllgaard, U., Lie, M., Odegard, O. R. (1976). Antithrombin assay with new chromogenic substrates (S-2238 and Chromozym TH). Thromb. Res., 11, 549CrossRefGoogle Scholar
  28. 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. 29.
    Delorme, A., Guyene, P. T., Corvol, P., Menard, J. (1976). Methodologie problems in plasma renin activity measurements. Am. J. Med., 61, 725CrossRefPubMedGoogle Scholar
  30. 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, 475CrossRefPubMedGoogle Scholar
  31. 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, 243CrossRefPubMedGoogle Scholar
  32. 32.
    Cramp, D. G. and Robertson, G. (1968). Fluorimetric assay of tri-glycerides by a semi-automated method. Anal. Biochem., 25, 246CrossRefPubMedGoogle Scholar
  33. 33.
    Burstein, M. and Samaille, J. (1960). Rapid method for cholesterol in serum a and ß lipoproteins. Clin. Chim. Acta, 5, 609CrossRefPubMedGoogle Scholar
  34. 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 11Google Scholar
  35. 35.
    Briggs, M. (1975). Biochemical effects of oral contraceptives. Adv. Steroid Biochem. Pharmacol., 5, 65Google Scholar
  36. 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: ScriptorGoogle Scholar
  37. 37.
    Briggs, M. and Briggs, M. H. (1977). Low dose oral contraceptives. OB/CYN Digest, February, 12–16Google Scholar
  38. 38.
    Rozenbaum, H. (1978). Low dose estrogen/progestogen combinations. Rév. Méd. (Paris), 19, 1821Google Scholar
  39. 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, 973PubMedGoogle Scholar
  40. 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, 193Google Scholar
  41. 41.
    Briggs, M. H. and Briggs (1977). Clinical and biochemical investigations of a variable-dose combined type oral contraceptive. Curr. Med. Res. Opin., 5, 212CrossRefGoogle Scholar
  42. 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, 43CrossRefGoogle Scholar
  43. 43.
    Lachnit-Fixson, U. (1979). The first three-stage preparation for hormonal contraception. Clinical results. Mauch. Med. Irochenschr., 121, 1421Google Scholar
  44. 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, 87PubMedGoogle Scholar
  45. 45.
    Woutersz, T. B. (1976). Three and one-half years’ experience with a lower-dose combination oral contraceptive. J. Reprod. Med., 16, 338PubMedGoogle Scholar
  46. 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, 618CrossRefGoogle Scholar

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© MTP Press Limited 1980

Authors and Affiliations

  • M. Briggs
  • M. Briggs

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