Metformin therapy for the reproductive and metabolic consequences of polycystic ovary syndrome
Open accessAbstract
Polycystic ovary syndrome (PCOS), the most common hormonal disorder among women of reproductive age, has various metabolic and reproductive consequences. Metformin was originally shown to lower testosterone levels in women with PCOS in the 1990s, an effect presumably related to its insulin sensitising actions. However, the precise mechanisms of metformin action in PCOS remain unclear and there is considerable heterogeneity in the clinical response to this therapy in women with PCOS. Recent evidence indicates that genetic factors may play a significant role in predicting response to metformin therapy in PCOS and future studies are needed to further identify women who are most likely to benefit from this therapy. At present, there is no clear evidence to support broad metformin use in PCOS. Well-designed prospective trials are needed to establish clear benefit for metformin use in the treatment of the reproductive and metabolic consequences associated with PCOS.
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Metformin's efficacy in improving clinical outcomes remains uncertain.
“However, the efficacy of metformin in terms of improving clinical outcomes remains uncertain (12).”
From Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome (2020) · cites this paper as [12]
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Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · see citing works
Franks, S. (1995) · New England Journal of Medicine · doi:10.1056/nejm199509283331307 · Cited by 2,463 · see citing works
The mechanisms of action of metformin
Rena, G., Hardie, D. G., & Pearson, E. R. (2017) · Diabetologia · doi:10.1007/s00125-017-4342-z · Cited by 2,287 · see citing works
Amenorrhea associated with bilateral polycystic ovaries
Stein, I. F., & Leventhal, M. L. (1935) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30642-6 · Cited by 2,121 · see citing works
Profound Peripheral Insulin Resistance, Independent of Obesity, in Polycystic Ovary Syndrome
Dunaif, A., Segal, K. R., Futterweit, W., & Dobrjansky, A. (1989) · Diabetes · doi:10.2337/diab.38.9.1165 · Cited by 1,967 · see citing works
Legro, R. S., Arslanian, S. A., Ehrmann, D. A., Hoeger, K. M., Murad, M. H., Pasquali, R., & Welt, C. K. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2350 · Cited by 1,919 · see citing works
Self-citationLegro, R. S. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.1.165 · Cited by 1,743 · see citing works
El-Mir, M.-Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., & Leverve, X. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.223 · Cited by 1,399 · see citing works
Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome.
Ehrmann, D. A., Barnes, R. B., Rosenfield, R. L., Cavaghan, M. K., & Imperial, J. (1999) · Diabetes Care · doi:10.2337/diacare.22.1.141 · Cited by 1,257 · see citing works
Self-citationPrevalence and Characteristics of the Metabolic Syndrome in Women with Polycystic Ovary Syndrome
Apridonidze, T., Essah, P. A., Iuorno, M. J., & Nestler, J. E. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1045 · Cited by 931 · see citing works
Correlation of Hyperandrogenism with Hyperinsulinism in Polycystic Ovarian Disease*
Burghen, G. A., Givens, J. R., & Kitabchi, A. E. (1980) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-50-1-113 · Cited by 922 · see citing works
Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP
Miller, R., Chu, Q., Xie, J., Foretz, M., Viollet, B., & Birnbaum, M. J. (2013) · Nature · doi:10.1038/nature11808 · Cited by 828 · see citing works
NESTLER, J. E., POWERS, L. P., MATT, D. W., STEINGOLD, K. A., PLYMATE, S. R., RITTMASTER, R. S., CLORE, J. N., & BLACKARD, W. G. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-72-1-83 · Cited by 815 · see citing works
Nestler, J. E., & Jakubowicz, D. J. (1996) · New England Journal of Medicine · doi:10.1056/nejm199608293350902 · Cited by 743 · see citing works
Balen, A. H., Morley, L. C., Misso, M., Franks, S., Legro, R. S., Wijeyaratne, C. N., Stener-Victorin, E., Fauser, B. C. J. M., Norman, R. J., & Teede, H. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmw025 · Cited by 705 · see citing works
Insulin resistance in nonobese patients with polycystic ovarian disease
CHANG, R. J., NAKAMURA, R. M., JUDD, H. L., & KAPLAN, S. A. (1983) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-57-2-356 · Cited by 704 · see citing works
Prevalence and Predictors of the Metabolic Syndrome in Women with Polycystic Ovary Syndrome
Ehrmann, D. A., Liljenquist, D. R., Kasza, K., Azziz, R., Legro, R. S., & Ghazzi, M. N. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1329 · Cited by 703 · see citing works
Self-citationTang, T., Lord, J. M., Norman, R. J., Yasmin, E., & Balen, A. H. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub5 · Cited by 698 · see citing works
Pasquali, R., Gambineri, A., Biscotti, D., Vicennati, V., Gagliardi, L., Colitta, D., Fiorini, S., Cognigni, G. E., Filicori, M., & Morselli-Labate, A. M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6738 · Cited by 635 · see citing works
Goodman, N. F., Cobin, R. H., Futterweit, W., Glueck, J. S., Legro, R. S., & Carmina, E. (2015) · Endocrine Practice · doi:10.4158/ep15748.dsc · Cited by 623 · see citing works
Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome
Legro, R. S., Kunselman, A. R., & Dunaif, A. (2001) · The American Journal of Medicine · doi:10.1016/s0002-9343(01)00948-2 · Cited by 622 · see citing works
McCartney, C. R., & Marshall, J. C. (2016) · New England Journal of Medicine · doi:10.1056/nejmcp1514916 · Cited by 619 · see citing works
Evidence for Distinctive and Intrinsic Defects in Insulin Action in Polycystic Ovary Syndrome
Dunaif, A. E., Segal, K. R., Shelley, D., Green, G., Dobrjansky, A., & Licholai, T. (1992) · Diabetes · doi:10.2337/diab.41.10.1257 · Cited by 544 · see citing works
Martin, K. A., Chang, R. J., Ehrmann, D. A., Ibáñez, L., Løbo, R. A., Rosenfield, R. L., Shapiro, J., Montori, V. M., & Swiglo, B. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2437 · Cited by 506 · see citing works
Self-citationEffect of Genetic Variation in the Organic Cation Transporter 1, OCT1, on Metformin Pharmacokinetics
Shu, Y., Brown, C., Castro, R. A., Shi, R., Lin, E., Owen, R., Sheardown, S., Yue, L., Burchard, E. G., Brett, C., et al. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100275 · Cited by 474 · see citing works
Nestler, J. E., & Jakubowicz, D. J. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.12.4431 · Cited by 394 · see citing works
Ehrmann, D. A., Cavaghan, M. K., Imperial, J., Sturis, J., Rosenfield, R. L., & Polonsky, K. S. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3722 · Cited by 346 · see citing works
Self-citationNESTLER, J. E., BARLASCINI, C. O., MATT, D. W., STEINGOLD, K. A., PLYMATE, S. R., CLORE, J. N., & BLACKARD, W. G. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-6-1027 · Cited by 338 · see citing works
Naderpoor, N., Shorakae, S., de Courten, B., Misso, M. L., Moran, L. J., & Teede, H. J. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv025 · Cited by 334 · see citing works
Diamanti‐Kandarakis, E., Kouli, C., Tsianateli, T. C., & Bergiele, A. T. (1998) · European Journal of Endocrinology · doi:10.1530/eje.0.1380269 · Cited by 320 · see citing works
Talbott, E. O., Clerici, A., Berga, S. L., Kuller, L. H., Guzick, D. S., Detre, K. M., Daniels, T. L., & Engberg, R. A. (1998) · Journal of Clinical Epidemiology · doi:10.1016/s0895-4356(98)00010-9 · Cited by 312 · see citing works
Jablonski, K. A., McAteer, J. B., de Bakker, P. I. W., Franks, P. W., Pollin, T. I., Hanson, R. L., Saxena, R., Fowler, S., Shuldiner, A. R., Knowler, W. C., et al. (2010) · Diabetes · doi:10.2337/db10-0543 · Cited by 271 · see citing works
Naderpoor, N., Shorakae, S., de Courten, B. V., Misso, M. L., Moran, L., & Teede, H. J. (2016) · Human Reproduction Update · doi:10.1093/humupd/dmv063 · Cited by 256 · see citing works
Metformin directly inhibits androgen production in human thecal cells
Attia, G. R., Rainey, W. E., & Carr, B. R. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(01)01975-6 · Cited by 254 · see citing works
Diamanti‐Kandarakis, E., Christakou, C. D., Kandaraki, E., & Economou, F. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0733 · Cited by 246 · see citing works
Variation in the glucose transporter gene SLC2A2 is associated with glycemic response to metformin
MetGen Investigators, Zhou, K., DPP Investigators, ACCORD Investigators, Yee, S. W., Seiser, E., van Leeuwen, N., Tavendale, R., Bennett, A. J., Groves, C. J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3632 · Cited by 238 · see citing works
Metformin has direct effects on human ovarian steroidogenesis
Mansfield, R., Galea, R., Brincat, M., Hole, D. R., & Mason, H. D. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(02)04925-7 · Cited by 235 · see citing works
Dunaif, A., & Graf, M. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113864 · Cited by 204 · see citing works
Hadwan, M. H., Almashhedy, L. A., & Alsalman, A. R. S. (2014) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-12-1 · Cited by 167 · see citing works
Nestler, J. E., & Jakubowicz, D. J. (1998) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-199805000-00018 · Cited by 135 · see citing works
Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review
Costello, M., Shrestha, B., Eden, J., JOHNSON, N. P., & Sjöblom, P. (2007) · Human Reproduction · doi:10.1093/humrep/dem005 · Cited by 132 · see citing works
Cosma, M., Swiglo, B. A., Flynn, D. N., Kurtz, D. M., LaBella, M. L., Mullan, R. J., Elamin, M. B., Erwin, P. J., & Montori, V. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2429 · Cited by 129 · see citing works
Heritability of variation in glycaemic response to metformin: a genome-wide complex trait analysis
Zhou, K., Donnelly, L. A., Yang, J., Li, M., Deshmukh, H., Zuydam, N. V., Ahlqvist, E., Spencer, C. C. A., Groop, L., Morris, A. D., et al. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70050-6 · Cited by 125 · see citing works
Hirsch, A., Hahn, D., Kempná, P., Hofer, G., Nuoffer, J.-M., Mullis, P. E., & Flück, C. E. (2012) · Endocrinology · doi:10.1210/en.2012-1145 · Cited by 109 · see citing works
Legro, R. S., Barnhart, H. X., Schlaff, W. D., Carr, B. R., Diamond, M. P., Carson, S. A., Steinkampf, M. P., Coutifaris, C., McGovern, P. G., Cataldo, N. A., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1736 · Cited by 102 · see citing works
Tang, T. H., Lord, J. M., Norman, R. J., Yasmin, E., & Balen, A. H. (2010) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub4 · Cited by 101 · see citing works
Pirwany, I. R., Yates, R. W. S., Cameron, I., & Fleming, R. (1999) · Human Reproduction · doi:10.1093/humrep/14.12.2963 · Cited by 100 · see citing works
Insulin Sensitivity after Metformin Suspension in Normal-Weight Women with Polycystic Ovary Syndrome
Palomba, S., Falbo, A. I., Russo, T., Manguso, F., Tolino, A., Zullo, F., Feo, P. D., & Orio, F. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0441 · Cited by 81 · see citing works
Kurzthaler, D., Hadziomerovic-Pekic, D., Wildt, L., & Seeber, B. E. (2014) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-12-98 · Cited by 66 · see citing works
Gambineri, A., Tomassoni, F., Gasparini, D. I., Rocco, A. D., Mantovani, V., Pagotto, U., Altieri, P., Sanna, S., Fulghesu, A. M., & Pasquali, R. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0145 · Cited by 53 · see citing works
Pau, C. T., Keefe, C. C., Duran, J. M., & Welt, C. K. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4021 · Cited by 50 · see citing works
Micić, D., POPOVIC, V. M., Nesović, M., Sumarac, M., Dragasević, M., Kendereški, A., Markovic, D., Djordjević, P., Manojlović, D., & Micić, J. (1988) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(88)90344-5 · Cited by 40 · see citing works
Lee, B. H., Indran, I. R., Tan, H. M., Li, Y., Zhang, Z., Li, J., & Yong, E. (2015) · Endocrinology · doi:10.1210/en.2015-1733 · Cited by 35 · see citing works
Schweighofer, N., Lerchbaum, E., Trummer, O., Theiler‐Schwetz, V., Pieber, T. R., & Obermayer-Pietsch, B. M. (2014) · Pharmacogenomics · doi:10.2217/pgs.13.223 · Cited by 16 · see citing works
Díaz, M., López‐Bermejo, A., Sánchez‐Infantes, D., Bassols, J., de Zegher, F., & Ibáñez, L. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.04.075 · Cited by 11 · see citing works
Pau, C. T., Cheang, K. I., Modi, B. P., Kasippillai, T., Keefe, C. C., Shulleeta, M., Evans, W. S., Pal, L., Strauss, J. F., Nestler, J. E., et al. (2016) · Pharmacogenomics · doi:10.2217/pgs-2016-0079 · Cited by 9 · see citing works
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Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome
Wang, J., Wu, D., Guo, H., & Li, M. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116940 · Cited by 322 · see citing works
Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome
Shang, Y., Zhou, H., Hu, M., & Feng, H. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa425 · Cited by 171 · see citing works
Javed, Z., Papageorgiou, M., Deshmukh, H., Rigby, A. S., Qamar, U., Abbas, J., Khan, A. Y., Kilpatrick, E. S., Atkin, S. L., & Sathyapalan, T. (2019) · Clinical Endocrinology · doi:10.1111/cen.13968 · Cited by 121 · see citing works
- Authors
- Sam, S., & Ehrmann, D. A.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Sam, Susan
- Venue
- Diabetologia
- Published
- 2017-08-03
- Volume
- 60
- Issue
- 9
- Pages
- 1656-1661
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2740419317
- Cited by
- 93
- References
- 56
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 3 · 2012: 1
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kovler Family Foundation
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- polycystic ovary syndrome, metformin, insulin sensitization, testosterone, insulin resistance, reproductive outcomes, metabolic effects, genetic predictors of treatment response, ovulation induction
- MeSH terms
- Body Composition, Female, Humans, Hypoglycemic Agents, Insulin Resistance, Metformin, Polycystic Ovary Syndrome, Reproduction
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