WITHDRAWN: Insulin-sensitising drugs for polycystic ovary syndrome.
BACKGROUND
Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is 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.


OBJECTIVE
To assess the effectiveness of insulin sensitising drugs in improving clinical and biochemical features of PCOS.


METHODS
We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008 ), the Cochrane Central Register of Controlled Trials (Cochrane Library, September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008).


METHODS
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.


METHODS
Thirty nine trials (3576 subjects) were included for analysis, 31 of them using metformin and involving 2625 participants.


RESULTS
Meta-analysis showed that metformin is effective in achieving ovulation in women with PCOS with odds ratios of 2.21(CI 1.57 to 3.10) for metformin versus placebo and 3.93(CI 2.32 to 6.65) for metformin and clomiphene versus clomiphene alone. An analysis of pregnancy rates suggests a significant treatment effect for metformin and clomiphene (OR 1.58, CI 1.20 to 2.07). Nevertheless, these benefits were not translated into live birth rates.Metformin has a significant effect in reducing fasting insulin levels (WMD -4.20 mIU/L, CI -7.68 to -0.73); however, the reduction was only significant in the non-obese group (BMI < 30 kg/m2). Treatment effect on serum testosterone concentration was observed; but the magnitude of the reduction was greater in the non-obese group compared with the obese group (WMD -1.79 versus. -0.30 nmol/L). Metformin has no effect on serum lipid profiles. Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported.


CONCLUSIONS
In agreement with the previous review, metformin is still of benefit in improving ovulation and pregnancy rates. However, metformin does not improve live birth whether it is used alone or in combination with clomiphene. In addition, metformin has limited effect on metabolic parameters, especially in obese women with PCOS. Therefore, the use of metformin in improvement of reproductive outcomes or in reducing the risk of developing metabolic syndrome in women with PCOS appears to be limited.
Tang
Thomas
T
Academic Unit of Paediatrics,Obstetrics and Gynaecology, St James University Hospital, Level 9, Gledhow Wing, Leeds, UK, LS9 7TF.
Lord
Jonathan M
JM
Norman
Robert J
RJ
Yasmin
Ephia
E
Balen
Adam H
AH
D000858:Anovulation / Q000188:drug therapy*; D002839:Chromans / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007294:Inositol / Q000627:therapeutic use; D008687:Metformin; D010062:Ovulation Induction; D011085:Polycystic Ovary Syndrome / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D013844:Thiazoles / Q000627:therapeutic use; D045162:Thiazolidinediones
D002839:Chromans; D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D007294:Inositol; D008687:Metformin