Insulin levels, insulin resistance and the use of metformin in polycystic ovary syndrome

Samantha K Hutchison, Sophia Zoungas and Helena J Teede
Med J Aust 2007; 186 (5): 268-269. || doi: 10.5694/j.1326-5377.2007.tb00889.x
Published online: 5 March 2007

To the Editor: We read with interest the recent article on insulin resistance,1 and we strongly support the argument that there is no current clinical utility to measuring fasting insulin levels. However, we are concerned about the statement that “otherwise well patients whom we see in practice are demanding (and receiving) metformin, or are being told they need it, particularly for polycystic ovary syndrome” (PCOS). Therapy in PCOS targets symptoms. Although Samaras et al imply that metformin is not required in “well patients”,1 the “well patient” is not defined. Most women with PCOS are, by definition, symptomatic, and most benefit from therapy.

We contend that, although measurement of insulin levels is not justified, insulin resistance is established in PCOS, and metformin is an effective treatment for women with PCOS. This contention is well supported in the literature. It is recognised that most women with PCOS have insulin resistance leading to hyperinsulinaemia and that insulin resistance plays a central aetiological role in the clinical manifestations of PCOS.2

However, as outlined by Samaras et al,1 the insulin level is not an appropriate marker for insulin resistance (a challenging parameter to measure in routine clinical practice) and, consequently, insulin resistance is not included in the diagnostic criteria for PCOS.

Strategies to decrease insulin resistance have proven effective in studies where patients are selected based on clinical diagnostic criteria for PCOS, not insulin levels. Indeed, reducing insulin resistance with both lifestyle change3 and insulin sensitisers4 is emerging as a promising treatment strategy.2 Although not yet “approved” for treating PCOS in Australia, metformin is an effective treatment for anovulatory cycles and infertility, and induces a mild decline in hyperandrogenaemia. This is supported by a recent Cochrane review.4,5 Increasingly, metformin is recommended as a first- or second-line therapy in anovulatory infertility4,6 because, in contrast to conventional infertility therapies, it does not increase multiple pregnancy rates.

In summary, metformin treatment in PCOS is supported by a significant evidence base, but the use of metformin should be based on clinical indications, independent of an individual’s insulin levels.

  • Samantha K Hutchison1
  • Sophia Zoungas2
  • Helena J Teede1,2

  • 1 The Jean Hailes Foundation for Women’s Health, Monash Institute of Health Services Research, Melbourne, VIC.
  • 2 Diabetes Unit, Southern Health, Melbourne, VIC.

  • 1. Samaras K, McElduff A, Twigg SM, et al. Insulin levels in insulin resistance: phantom of the metabolic opera? Med J Aust 2006; 185: 159-161. <MJA full text>
  • 2. Teede HJ, Hutchison SK, Zoungas S, Meyer C. Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS. Endocrine 2006; 30: 45-53.
  • 3. Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. J Clin Endocrinol Metab 1999; 84: 1470-1474.
  • 4. Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, d-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003; (3): CD003053.
  • 5. Teede HJ, Meyer C, Norman RJ. Insulin-sensitisers in the treatment of polycystic ovary syndrome. Expert Opin Pharmacother 2005; 6: 2419-2427.
  • 6. Palomba S, Orio F Jr, Falbo A, et al. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 4068-4074.


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