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PubMed2003

Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogenaemia and insulin resistance. Hyperinsulinaemia is known to be associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome. OBJECTIVES: To assess the effectiveness of insulin sensitising drugs in improving clinical and biochemical features of PCOS. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (December 2002), the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2002), MEDLINE (January 1966 to December 2002), and EMBASE (January 1985 to December 2002). SELECTION CRITERIA: Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent. DATA COLLECTION AND ANALYSIS: Performed by two reviewers, one blinded to information that could have identified the authors, publisher or results of each study. Fifteen trials were included for analysis, 13 of them using metformin and involving 543 participants. MAIN RESULTS: Meta-analysis showed that metformin is effective in achieving ovulation in women with PCOS with odds ratios of 3.88 (CI 2.25 to 6.69) for metformin versus placebo and 4.41 (CI 2.37 to 8.22) for metformin and clomifene versus clomifene alone. An analysis of pregnancy rates suggests a significant treatment effect for metformin and clomifene (OR 4.40, CI 1.96 to 9.85). Metformin has a significant effect in reducing fasting insulin levels (WMD -5.37, CI -8.11 to -2.63), blood pressure and low-density lipoprotein cholesterol (LDL). There was no evidence of effect on body mass index or waist:hip ratio. Metformin was associated with a significantly higher incidence of nausea, vomiting and other gastrointestinal disturbance, but no serious adverse effects were reported. REVIEWER'S CONCLUSIONS: Metformin is an effective treatment for anovulation in women with PCOS. Its choice as a first line agent seems justified, and there is some evidence of benefit on parameters of the metabolic syndrome. Ovulation rates are higher when combined with clomifene (76% versus 46% when used alone), but there is no evidence to indicate whether there is an increased multiple pregnancy rate with this combination. There is no data regarding its safety in long-term use in young women. It should be used as an adjuvant to general lifestyle improvements, and not as a replacement for increased exercise and improved diet.

Anovulation↗
PubMed2005

The PPAR(gamma) K422Q mutation does not contribute to troglitazone inefficiency in colon cancer treatment.

Peroxisome proliferator-activated receptor gamma (PPAR(gamma)) ligands inhibit cell growth of colorectal cancer cells in most experimental models, but no significant effect could be observed in patients with colorectal cancer. We therefore, screened human colorectal tumors to determine the prevalence of the PPAR(gamma) K422Q loss-of-function mutation, recently identified in 50% of colonic cancer cell lines. A sensitive allele-specific real-time amplification assay was developed and 170 colorectal primary tumors and 12 liver metastasis were analyzed. We did not find the K422Q mutation in any of these samples. We can therefore exclude this alteration as a mechanism of resistance to PPAR(gamma) ligands in patients with colon cancer.

Adult↗