Skip to main content
  • 1392 Accesses

Abstract

Polycystic ovary syndrome (PCOS) is associated with about 75 % of all cases of anovulatory infertility. Insulin resistance is frequently associated with PCOS, occurring in 80 % of women with PCOS and central obesity, but also in 30–40 % of lean women with PCOS. As a result of the reduction in insulin sensitivity, hyperinsulinaemia is invoked as a compensatory mechanism and this is of prime importance in the pathophysiology of PCOS as hyperinsulinaemia, which is significantly exacerbated by obesity, is a key factor in the pathogenesis of hyperandrogenism. Weight loss often seems to be an unsurmountable object for the obese patient with PCOS and the alternative possibility of using insulin lowering drugs, particularly metformin, is theoretically attractive. Although metformin as a mono-agent is capable of improving menstrual frequency and restoring ovulation in patients who have oligo-anovulation and PCOS, when used as first line therapy and compared to clomifene (CC), it fairs very poorly. In a large North American randomised controlled trial, CC was found to be superior to metformin as there was a significant difference in the number of clinical pregnancies and live full-term singleton births (22.6 % vs 7.2 %) using CC and metformin respectively. Insulin sensitizers should not be used as first-choice agents for induction of ovulation in women with PCOS and their administration does not appear to decrease the incidence of early pregnancy losses. The combination of metformin and CC is no better than CC alone except perhaps in CC resistant patients. Evidence for a possible role for long-term metformin treatment for the prevention of the long-term sequelae of PCOS is awaited.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1998;83:2694–8.

    CAS  PubMed  Google Scholar 

  2. Carmina E, Lobo RA. Polycystic ovary syndrome: arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab. 1999;84:1897–9.

    Article  CAS  PubMed  Google Scholar 

  3. Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LA. The insulin-related ovarian regulatory system in health and disease. Endoc Rev. 1999;20:535–82.

    Article  CAS  Google Scholar 

  4. Homburg R. Adverse effect of luteinizing hormone on fertility: fact or fantasy. Baillieres Clin Obstet Gynaecol. 1996;12:555.

    Article  Google Scholar 

  5. Dale O, Tanbo T, Haug E, Abyholm T. The impact of insulin resistance on the outcome of ovulation induction with low-dose FSH in women with polycystic ovary syndrome. Hum Reprod. 1998;13:567–70.

    Article  CAS  PubMed  Google Scholar 

  6. Hamilton-Fairley D, Kiddy D, Watson H, et al. Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary treated with low dose gonadotrophin. Br J Obstet Gynaecol. 1992;99:128–31.

    Article  CAS  PubMed  Google Scholar 

  7. White DM, Polson DW, Kiddy D, et al. Induction of ovulation with low-dose gonadotrophins in polycystic ovary syndrome: an analysis of 109 pregnancies in 225 women. J Clin Endocrinol Metab. 1996;81:3821–4.

    CAS  PubMed  Google Scholar 

  8. Kiddy DS, Hamilton-Fairley D, Bush A, et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 1992;36:105–11.

    Article  CAS  Google Scholar 

  9. Pasquali R, Antenucci D, Casmirri F, et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab. 1989;68:173–9.

    Article  CAS  PubMed  Google Scholar 

  10. Clark AM, Ledger W, Galletly C, et al. Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod. 1995;10:2705–12.

    Article  CAS  PubMed  Google Scholar 

  11. Velazquez EM, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol. 1997;90:392–5.

    Article  CAS  PubMed  Google Scholar 

  12. Fleming R, Hopkinson ZE, Wallace AM, et al. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002;87:569–74.

    Article  CAS  PubMed  Google Scholar 

  13. Mansfield R, Galea R, Brincat M, et al. Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril. 2003;79:956–62.

    Article  PubMed  Google Scholar 

  14. Harbourne L, Fleming R, Lyall H, et al. Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. Lancet. 2003;361:1894–901.

    Article  Google Scholar 

  15. Nestler JE, Stovall D, Akhter N, et al. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril. 2002;77:209–15.

    Article  PubMed  Google Scholar 

  16. Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551–66.

    Article  CAS  PubMed  Google Scholar 

  17. Zain MM, Jamaluddin R, Ibrahim A, Norman R. Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction, achievement of pregnancy, and live birth in Asian women with polycystic ovary syndrome: a randomized controlled trial. Fertil Steril. 2009;91:514–21.

    Article  CAS  PubMed  Google Scholar 

  18. Tang T, Glanville J, Hayden CJ, White D, Barth JH, Balen AH. Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study. Hum Reprod. 2006;21:80–9.

    Article  PubMed  Google Scholar 

  19. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2010;20(1):CD003053.

    Google Scholar 

  20. Thessaloniki ESHRE/ASRM- sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23:462–77.

    Article  Google Scholar 

  21. Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. Br Med J. 2006;332:1485–8.

    Article  CAS  Google Scholar 

  22. Vandermolen DT, Ratts VS, Evans WS, et al. Metformin increases the ovulatory rate and pregnancy rate with clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone. Fertil Steril. 2001;75:310–5.

    Article  CAS  PubMed  Google Scholar 

  23. George SS, George K, Irwin C, et al. Sequential treatment of metformin and clomiphene citrate in clomiphene resistant women with polycystic ovary syndrome: a randomized, controlled trial. Hum Reprod. 2003;18:299–304.

    Article  CAS  PubMed  Google Scholar 

  24. De Leo V, la Marca A, Ditto A, et al. Effects of metformin on gonadotropin-induced ovulation women with polycystic ovary syndrome. Fertil Steril. 1999;72:282–5.

    Article  PubMed  Google Scholar 

  25. Kjotrod SB, von During V, Carlsen SM. Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome: a prospective, randomized, double-blind study. Hum Reprod. 2004;19:1315–22.

    Article  CAS  PubMed  Google Scholar 

  26. Vanky E, Stridsklev S, Heimstad R, et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab. 2010;95:E448–55.

    Article  CAS  PubMed  Google Scholar 

  27. Homburg R. Polycystic ovary syndrome in adolescence – a therapeutic conundrum. Hum Reprod. 2004;19:1039–42.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Homburg, R. (2014). Insulin Lowering Agents. In: Ovulation Induction and Controlled Ovarian Stimulation. Springer, Cham. https://doi.org/10.1007/978-3-319-05612-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-05612-8_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-05611-1

  • Online ISBN: 978-3-319-05612-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics