Androgenic properties of progestogens used in oral contraceptives

  • J. Spona


Recent reports claimed 3-keto-desogestrel to exert less androgen-related side-effects than levonorgestrel. These claims were based on data obtained from receptor assays performed as single determinations. We were prompted to investigate androgenic actions since our own clinical experience with these two progestins did not suggest differences in androgen-related side-effects. In addition, actions of cyproterone acetate (CPA) were studied. Relative binding affinities for the androgen receptor were investigated in cytosol samples of mice kidneys. β-glucuronidase activities were determined in kidneys of adult mice treated subcutaneously with 0.05, 0.5 and 1.5 mg of progestational agents for 7 days.

RBA for the androgen receptor of DOG, LNg and CPA were 0.316 ± 0.092, 0.195 ± 0.053 and 0.204 ± 0.022, respectively, as registered in seven different experiments. Statistical analysis of data revealed significantly greater RBA for DOG than for LNg (p < 0.02). No differences in β-glucuronidase activities between DOG and LNg were noted for 0.05 and 0.5mg doses whereas a significantly greater enzyme stimulation by DOG was registered for the 1.5mg dose (p< 0.005).

CPA was found to exert synandrogenic action on β-glucuronidase activities at the lower dose level and antiandrogenic action at the higher dose levels. The present data suggest that 3-keto-desogestrel exerts more pronounced androgenic actions on target tissues than levonorgestrel. Clinical data indicate no greater differences in andro-gen-related side-effects between oral contraceptives with 3-keto-desogestrel or levonorgestrel.


Androgen Receptor Oral Contraceptive Cyproterone Acetate Fertility Control Androgenic Action 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brotherton, J. (1976). Biological assessment. In Brotherton, J. (ed.). Sex Hormone Pharmacology, pp. 43–78. (London: Academic Press)Google Scholar
  2. 2.
    Briggs, M. H. and Briggs, M. (1976). Pharmacology. In Briggs, M. H. and Briggs, M. (eds.). Biochemical Contraception, pp. 69–72. (London: Academic Press)Google Scholar
  3. 3.
    Edgren, R. A., Jones, R. C., Clancy, D. P. and Nagra, C. L. (1968). The biological effects of norgestrel alone and in combination with ethinyl-estradiol. J. Reprod. Fertil., 5, 13Google Scholar
  4. Viinikka, L., Ylikorkala, O., Vihko, R., Wijnand, H. P., Booij, M. and van der Veen, F. (1979). Metabolism of a new synthetic progestagen, Org. 2969, in female volunteers. Pharmacokinetics after an oral dose. Eur. J. Clin. Pharmacol, 15, 349PubMedCrossRefGoogle Scholar
  5. 5.
    De Jager, E. (1982). A new progestagen for oral contraception. Contracept. Deliv. Syst., 3, 11PubMedGoogle Scholar
  6. 6.
    Gupta, C., Bullock, L. and Bardin, C. W. (1978). Further studies on the androgenic, antiandrogenic and synandrogenic actions of progestins. Endocrinology, 120, 736CrossRefGoogle Scholar
  7. 7.
    Bergink, E. W., Hamburger, A. D., De Jager, E. and van der Vies, J. (1981). Binding of a contraceptive progestagen ORG 2669 and its metabolites to receptor proteins and human SHBG. J. Ster. Biochem., 14, 175CrossRefGoogle Scholar
  8. 8.
    Spona, J., Ulm, R., Bieglmayer, C. and Husslein, P. (1979). Hormone serum levels and hormone receptor contents of endometria in women with normal menstrual cycles and patients bearing endometrial carcinoma. Gynecol. Obstet. Invest., 10, 71PubMedCrossRefGoogle Scholar
  9. 9.
    Fishman, W. H. (1974). β-Glucuronidase. In Bergmeyer, H. U. (ed.). Methoden der Enzymatischen Analyse, Vol. 1,3. Auflage, pp. 964–979. (Berlin: Verlag Chemie)Google Scholar
  10. 10.
    Edgren, R. A., Jones, R. C. and Peterson, D. L. (1967). A biological classification of progestational agents. Fertil. Steril, 18, 238PubMedGoogle Scholar
  11. 11.
    Suchowsky, G. K. and Junkmann, K. (1961). A study of the virilizing effect of progestagens on the female rat fetus. Endocrinology, 68, 341CrossRefGoogle Scholar
  12. 12.
    Revesz, C., Chappel, C. I. and Gaudry, R. (1960). Virilisation by progestagen of external genitalia of female fetus. Endocrinology, 66, 140CrossRefGoogle Scholar
  13. 13.
    de Visser, J., de Jager, E., De Jongh, H., van der Vies, J. and Zeelen, F. (1975). Pharmacological profile of a new orally active progestational steroid: Org. 2969. Acta Endocrinol. (Copenh.) (Suppl.), 199, 405Google Scholar
  14. 14.
    Bullock, L. P., Bardin, C. W. and Sherman, M. R. (1978). Androgenic, antiandrogenic actions of progestins: role of steric and allosteric interactions with androgen receptors. Endocrinology, 103, 1768PubMedCrossRefGoogle Scholar
  15. 15.
    Gang, S., Anderson, K. M. and Liao, S. (1969). Receptor proteins for androgens. On the role of specific proteins in selective retention for 17β-hydroxy-5α-androstan-e-one by rat ventral prostate in vivo and in vitro. J. Biol. Chem., 244, 6584Google Scholar
  16. 16.
    Baulieu, E. E. and Jung, I. (1970). A prostatic cytosol receptor. Biochem. Biophys. Res. Commun., 38, 599PubMedCrossRefGoogle Scholar
  17. 17.
    Mowszowicz, I, Bieber, D. E., Chung, K. W., Bullock, L. P. and Bardin, C. W. (1974). Synandrogenic and antiandrogenic effect of progestins: comparison with nonprogestational antiandrogens. Endocrinology, 95, 1589PubMedCrossRefGoogle Scholar
  18. 18.
    Spona, J. (1982). Erlauben Rezeptorassays Aussagen über die biologische Wirksamkeit von Gestagene? In Hammerstin, J. (ed.). Aktuelle Aspekte der Hormonalen Kontrazeption. (Amsterdam: Excerpta Medica)Google Scholar
  19. 19.
    Brown, T. R., Bullock, L. and Bardin, C. W. (1979). In vitro and in vivo binding of progestins to the androgen receptor of mouse kidney: correlation with biological activities. Endocrinology, 105, 1281PubMedCrossRefGoogle Scholar

Copyright information

© MTP Press Limited 1984

Authors and Affiliations

  • J. Spona

There are no affiliations available

Personalised recommendations