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Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome
Abstract
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.
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Citations
Cited by
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Self-citationEscobar-Morreale, H. F., Carmina, E., Dewailly, D., Gambineri, A., Kelestimur, F., Moghetti, P., Pugeat, M., Qiao, J., Wijeyaratne, C. N., Witchel, S. F., et al. (2012) · Human Reproduction Update · doi:10.1093/humupd/dmr042 · Cited by 494
Self-citationPalomba, S., Falbo, A., Zullo, F., & Orio, F. (2009) · Endocrine Reviews · doi:10.1210/er.2008-0030 · Cited by 426
Tang, T., Glanville, J., Hayden, C. J., White, D., Barth, J. H., & Balen, A. H. (2006) · Human Reproduction · doi:10.1093/humrep/dei311 · Cited by 335
Self-citationMetformin therapy and clinical uses
Scarpello, J. H., & Howlett, H. C. (2008) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2008.027 · Cited by 318
The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome
Blank, S. K., McCartney, C. R., & Marshall, J. C. (2006) · Human Reproduction Update · doi:10.1093/humupd/dml017 · Cited by 301
Morley, L. C., Tang, T., Yasmin, E., Norman, R. J., & Balen, A. H. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub6 · Cited by 296
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Costello, M. F., Shrestha, B., Eden, J., Johnson, N., & Moran, L. J. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005552.pub2 · Cited by 197
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Neuroendocrine dysfunction in polycystic ovary syndrome
Burt Solorzano, C. M., Beller, J. P., Abshire, M. Y., Collins, J. S., McCartney, C. R., & Marshall, J. C. (2012) · Steroids · doi:10.1016/j.steroids.2011.12.007 · Cited by 173
“In addition, treatments that reduce hyperinsulinemia have been shown to decrease androgen levels and restore normal ovulation in women and adolescents with PCOS [31,32].”
BackgroundRachoń, D., & Teede, H. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.09.026 · Cited by 161
The management of insulin resistance in polycystic ovary syndrome
Teede, H. J., Hutchison, S. K., & Zoungas, S. (2007) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2007.08.001 · Cited by 135
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Self-citationGlintborg, D., Andersen, M., Richelsen, B., & Bruun, J. M. (2009) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2009.03523.x · Cited by 78
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RetractedPharmacological Approaches to Controlling Cardiometabolic Risk in Women with PCOS
Cignarella, A., Mioni, R., Sabbadin, C., Dassie, F., Parolin, M., Vettor, R., Barbot, M., & Scaroni, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249554 · Cited by 36
Javed, Z., Papageorgiou, M., Madden, L. A., Rigby, A. S., Kilpatrick, E. S., Atkin, S. L., & Sathyapalan, T. (2020) · Endocrine Connections · doi:10.1530/ec-20-0173 · Cited by 24
Bahadur, A., Arora, H., Ravi, A. K., Naithani, M., Bahurupi, Y., Chaturvedi, J., Ajmani, M., & Mundhra, R. (2021) · Cureus · doi:10.7759/cureus.15510 · Cited by 22
Aghahosseini, M., Aleyaseen, A., Safdarian, L., Moddaress-Hashemi, S., Mofid, B., & Kashani, L. (2010) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-010-1579-x · Cited by 12
Insulin levels, insulin resistance and the use of metformin in polycystic ovary syndrome
Hutchison, S. K., Zoungas, S., & Teede, H. J. (2007) · Medical Journal of Australia · doi:10.5694/j.1326-5377.2007.tb00889.x · Cited by 4
Metadata
- Authors
- Tang, T., Norman, R. J., Balen, A. H., & Lord, J. M.
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- John Wiley & Sons, Ltd
- Published
- 2003-04-22
- Issue
- 3
- Pages
- CD003053-CD003053
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- OpenAlex
- W1898761049
- Cited by
- 369
- References
- 0
- Type
- reference entry
- Language
- en
- Open access
- closed
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