Skip to main content
SpringerLink
Log in

Reduction of endogenous, ovarian and adrenal androgens with ketoconazole does not alter insulin response in the polycystic ovary syndrome

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Several different strategies were used to investigate the relationship between hyperandrogenism and hyperinsulinemia associated with polycystic ovary syndrome. Ketoconazole was given orally(400 mg/day) for 9 months to evaluate the effect of reduction in ovarian and adrenal androgens on insulin response (oral glucose tolerance test) in 35 women with polycystic ovary syndrome. Androgenic steroids (testosterone, androstenedione, dehydroepiandrosterone sulphate/and free testosterone index) decreased (p<0.01), but basal insulinemia, maximum peak insulin, and insulin/glucose ratio showed no significant changes. One month after treatment was stopped, free testosterone index, and serum concentrations of androstenedione and testosterone, increased (p<0.05), but no alterations were noted in insulin parameters. Body mass index was stable throughout the ten-month study period. Our findings suggest that endogenous androgens, no matter whether they are of ovarian or adrenal origin, do not play a major role in the modulation of hyperinsulinemia in patients with polycystic ovary syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barbieri R.L., Smith S., Ryan K.J. The role of hyperinsulinemia in the pathogenesis of ovarian hyperandrogenism. Fertil. Steril. 49:197, 1988.

    Google Scholar 

  2. Barbieri R.L. Hyperinsulinemia and ovarian hyperandrogenism. Cause and effect. Endocrinol. Metab. Clin. North Am. 17: 685, 1989.

    Google Scholar 

  3. Vidal-Puig A., Muñoz-Torres M., Escobar-Jiménez F. New approaches to the definition and diagnostic criteria in the polycystic ovary syndrome. Med. Clin. (Barc.) 100: 389, 1993.

    CAS  Google Scholar 

  4. Rittmaster R.S., Deshwal N., Lehman L. The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of Polycystic Ovarian Syndrome. J. Clin. Endocrinol. Metab. 76: 1295, 1993.

    CAS  PubMed  Google Scholar 

  5. Tropeano G., Lucisano A., Liberale I., Barini A., Vuolo I.P., Martino G., Menini E., Dell’Acqua S. Insulin, C-Peptide, Androgens, and ß-Endorphin response to oral glucose in patients with Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab. 78: 305, 1994.

    CAS  PubMed  Google Scholar 

  6. Conway G.S., Clark P.M.S., Wong D. Hyperinsulinemia in the polycystic ovary syndrome confirmed with a specific immunoradiometric assay for insulin. Clin. Endocrinol. (Oxf.) 38: 219, 1993.

    Article  CAS  Google Scholar 

  7. Geffner M.E., Kaplan S.A., Bersch N., Golde D.W., Lanaw E.M., Chang R.J. Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion. Fertil. Steril. 45: 327, 1986.

    CAS  PubMed  Google Scholar 

  8. Dunaif A., Green G., Futterweit W., Dobrjansky A. Supression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 70: 699, 1990.

    Article  CAS  PubMed  Google Scholar 

  9. Dale P.O., Tanbo T., Djoselan O., Jervell J., Abyholm T. Persistence of hyperinsulinemia in polycystic ovary sindrome after ovarian suppression by gonadotropin releasing hormone agonist. Acta Endocrinol. (Copenh.) 126: 132, 1992.

    CAS  Google Scholar 

  10. Martikainen H., Heikkinen J., Ruokonen A., Kauppila A. Hormonal and clinical effects of ketoconazole in hirsute women. J. Clin. Endocrinol. Metab. 66: 987, 1988.

    Article  CAS  PubMed  Google Scholar 

  11. Venturoli S., Fabbri R., Dal Prato L., Mantovani B., Capelli M., Magrini O., Flamigni C. Ketoconazole therapy for women with acne and/or hirsutism. J. Clin. Endocr. Metab. 71: 335, 1990.

    Article  CAS  PubMed  Google Scholar 

  12. Pepper G.M., Poretsky L., Gabrilove J.L., Ariton M.M. Ketoconazole reverses hyperandrogenism in a patient with insulin resistance and acanthosis nigricans. J. Clin. Endocrinol. Metab. 65: 1047,1987.

    Article  CAS  PubMed  Google Scholar 

  13. Akalin S. Effects of ketoconazole in hirsute women. Acta Endocrinol. (Copenh.) 124: 19, 1992.

    Google Scholar 

  14. Muñoz-Torres M., Vidal-Puig A., Tercedor J., Diaz J., Céspedes S., Escobar-Jiménez F. Hyperandrogenism, insulin resistance and acantosis nigricans: Effect of low dose ketoconazole therapy. Endocrinologia 37: 57, 1990.

    Google Scholar 

  15. Feldman D. Ketoconazole and other imidazole derivatives as inhibitors of steroidogenesis. Endocr. Rev. 7: 409, 1986.

    Article  CAS  PubMed  Google Scholar 

  16. Muñoz-Torres M., Vidal-Puig A., Escobar-Jiménez F., Hernando I., Diaz de Madrid J., Cespedes S. Hyperinsulinaemia in women with hyperandrogenism. Endocrinologia 37: 202, 1990.

    Google Scholar 

  17. Vidal-Puig A., Muñoz-Torres M., Escobar-Jiménez F., Ruiz-Requena M.E., Garcia-Calvente C., Torres-Vela E. Dehydroepiandrosterone sulfate and other influencing factors of sex hormone binding globulin levels in the hirsute patient. J. Steroid. Biochem. Molec. Biol. 42: 607, 1992.

    Article  CAS  PubMed  Google Scholar 

  18. Pollock M.A., Ratcliffe W. Laboratory comparison of three indices of free testosterone concentration. Ann. Clin. Biochem. 24 (Suppl. 1): 182, 1987.

    Google Scholar 

  19. Daneshmend T.K., Warnock D.W., Ene M.D., Johnson E.M., Potten M.R. Influence of food on the pharmacokinetics of ketoconazole. Antimicrob. Agents. Chemother. 25: 1, 1984.

    Article  CAS  Google Scholar 

  20. Daneshmend T.K., Warnock D.W. Clinical pharmacokinetics of ketoconazole. Clin. Pharmacokin. 14: 13, 1988.

    Article  CAS  Google Scholar 

  21. Speiser P.W., Serrat J., New M.I. Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxilase deficiency. J. Clin. Endocrinol. Metab. 75: 1421, 1992.

    CAS  PubMed  Google Scholar 

  22. Vidal-Puig A., Muñoz-Torres M., Escobar-Jiménez F. Hyperinsulinaemia in hyperandrogenic states. Endocrinologia 39: 13, 1992.

    Google Scholar 

  23. O’Meara N.M., Blackman J.D., Ehrmann D.A., Barnes R.B., Jaspan J.B., Rosenfield R.L., Polonsky K.S. Defects in ß-cell function in functional ovarian hyperandrogenism. J. Clin. Endocrinol. Metab. 76: 1241, 1993.

    PubMed  Google Scholar 

  24. Stuart C.A., Prince M.J., Peters E.J., Meyer III J. Hyperinsulinaemia and hyperandrogenemia: in vivo androgen response to insulin infusion. Obstet. Gynecol. 69: 921, 1987.

    CAS  PubMed  Google Scholar 

  25. Smith S., Ravnikar V.A., Barbieri R.L. Androgen and insulin response to an oral glucose challenge in hyperandrogenic women. Fertil. Steril. 48: 72, 1987.

    CAS  PubMed  Google Scholar 

  26. Falcone T., Finegood D.T., Fantus G., Morris D. Androgen response to endogenous insulin secretion during the frequently sampled intravenous glucose tolerance test in normal and hyperandrogenic women. J. Clin. Endocrinol. Metab. 71: 1653, 1990.

    Article  CAS  PubMed  Google Scholar 

  27. Hubert G.D., Schriock E.D., Givens J.R., Buster J.E. Supression of circulating delta 4 androstendione and dehydroepiandrosterone sulfate during oral glucose tolerance test in normal females. J. Clin. Endocrinol. Metab. 73: 781, 1991.

    Article  CAS  PubMed  Google Scholar 

  28. Elkind-Hirsch K.E., Valdes C., McConnell T.G., Mallinak L.R. Androgen response to acutely increased endogenous insulin levels in hyperandrogenic and normal cycling women. Fertil. Steril. 55: 486, 1991.

    CAS  PubMed  Google Scholar 

  29. Nestler J.E., Barlascini C.O., Matt D.W. Supression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 68: 1027, 1989.

    Article  CAS  PubMed  Google Scholar 

  30. Nestler J.E., Singh R., Matt D.W., Clore J.N., Blackard W.G. Suppression of serum insulin level by diazoxide does not after serum testosterone or sex hormone binding globulin levels in healthy non obese women. Am. J. Obstet. Gynecol. 163: 1243, 1990.

    Article  CAS  PubMed  Google Scholar 

  31. Poretsky L., Kalin M.F. The gonadotropic function of insulin. Endocr. Rev. 8: 132, 1987

    Article  CAS  PubMed  Google Scholar 

  32. Poretsky L. On the paradox of insulin induced hyperandrogenism in insulin resistant states. Endocr. Rev. 12: 3, 1991.

    Article  CAS  PubMed  Google Scholar 

  33. Nestler J.E., Straus III J.F. Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocr. Metab. Clin. North. Am. 20: 807, 1991.

    CAS  Google Scholar 

  34. Schriock E.D., Buffington C.K., Hubert G.D. Divergent correlations of circulating dehy-droepiandrosterone sulfate and testosterone with insulin levels and insulin receptor binding. J. Clin. Endocrinol. Metab. 66: 1329, 1988.

    Article  CAS  PubMed  Google Scholar 

  35. Nestler J.E., Clore N.J., Strauss J.F., Blackard W.G. The effects of hyperinsulinemia on serum testosterone, progesterone, dehydroepiandrosterone sulfate, and cortisol levels in normal women an in a woman with hyperandrogenism, insulin resistance, and acanthosis nigricans. J. Clin. Endocrinol. Metab. 64: 180, 1987.

    Article  CAS  PubMed  Google Scholar 

  36. Nestler J.E., Usiskin K.S., Barlascini C.O., Welty D.F., Clore J.N., Blackard W.G. Suppression of serum dehydroepiandrosterone sulfate levels by insulin: an evaluation of possible mechanisms. J. Clin. Endocrinol. Metab. 69: 1040, 1989.

    Article  CAS  PubMed  Google Scholar 

  37. Nestler J.E. Sex Hormone-Binding Globulin: a marker for hyperinsulinemia and/or insulin resistance? (Editorial). J. Clin. Endocrinol. Metab. 76: 273, 1993.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine I, Endocrine Division, University of Granada Hospital, Granada, Spain

    A. Vidal-Puig,  Manuel Muñoz-Torres, C. Garcia-Calvente, E. Jodar-Gimeno & F. Escobar-Jiménez

  2. Department of Epidemiology, University of Granada Hospital, Granada, Spain

    P. Lardelli

  3. Department of Biochemistry, University of Granada Hospital, Granada, Spain

    M. E. Ruiz-Requena

Authors
  1. A. Vidal-Puig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel Muñoz-Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Garcia-Calvente
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Jodar-Gimeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Lardelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. E. Ruiz-Requena
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Escobar-Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was supported by a grant from the Education and Science Council of the Andalusian Regional Government.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vidal-Puig, A., Muñoz-Torres, M., Garcia-Calvente, C. et al. Reduction of endogenous, ovarian and adrenal androgens with ketoconazole does not alter insulin response in the polycystic ovary syndrome. J Endocrinol Invest 17, 647–652 (1994). https://doi.org/10.1007/BF03349680

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03349680

Key-words

Search

Navigation