Download PDF
Semin Reprod Med 2014; 32(04): 323-330
DOI: 10.1055/s-0034-1375186
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Metformin and Other Insulin Sensitizers in Polycystic Ovary Syndrome

Bala Bhagavath
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York
,
Wendy Vitek
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York
,
John Queenan
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York
,
Kathleen Hoeger
1   Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, New York
› Author Affiliations
Further Information

Publication History

Publication Date:
11 June 2014 (online)

    Permissions and Reprints

Abstract

Polycystic ovary syndrome (PCOS) is a complex disorder affecting a substantial group of women from adolescent to menopausal age groups. A substantial subgroup of these women exhibits increased insulin resistance. Insulin resistance is difficult to establish in clinical practice and many surrogate tests are available, although their value in the clinical setting is uncertain. The QUICKI method is an inexpensive and easy test to administer and is probably the best test to be used in PCOS patients, preferably in a clinical trial context. There is considerable evidence that insulin-sensitizing agents are not contributory to infertility management in the majority of women with PCOS. Currently, there is no evidence that cardiovascular morbidity is decreased by long-term use of insulin sensitizers in PCOS women.

Keywords

PCOS - insulin sensitizers - treatment - infertility
 

  • References

  • 1 Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181-191
    PubMedGoogle Scholar
  • 2 Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab 1987; 65 (3) 499-507
    CrossrefPubMedGoogle Scholar
  • 3 Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294 (1) E15-E26
    CrossrefPubMedGoogle Scholar
  • 4 DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005; 83 (5) 1454-1460
    CrossrefPubMedGoogle Scholar
  • 5 Carmina E, Oberfield SE, Lobo RA. The diagnosis of polycystic ovary syndrome in adolescents. Am J Obstet Gynecol 2010; 203 (3) e1-e5
    CrossrefPubMedGoogle Scholar
  • 6 Goverde AJ, van Koert AJ, Eijkemans MJ , et al. Indicators for metabolic disturbances in anovulatory women with polycystic ovary syndrome diagnosed according to the Rotterdam consensus criteria. Hum Reprod 2009; 24 (3) 710-717
    PubMedGoogle Scholar
  • 7 Moran L, Teede H. Metabolic features of the reproductive phenotypes of polycystic ovary syndrome. Hum Reprod Update 2009; 15 (4) 477-488
    CrossrefPubMedGoogle Scholar
  • 8 Kirschner MA, Samojlik E, Drejka M, Szmal E, Schneider G, Ertel N. Androgen-estrogen metabolism in women with upper body versus lower body obesity. J Clin Endocrinol Metab 1990; 70 (2) 473-479
    CrossrefPubMedGoogle Scholar
  • 9 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18 (6) 774-800
    CrossrefPubMedGoogle Scholar
  • 10 Baillargeon JP, Nestler JE. Commentary: polycystic ovary syndrome: a syndrome of ovarian hypersensitivity to insulin?. J Clin Endocrinol Metab 2006; 91 (1) 22-24
    CrossrefPubMedGoogle Scholar
  • 11 Dunaif A, Thomas A. Current concepts in the polycystic ovary syndrome. Annu Rev Med 2001; 52: 401-419
    CrossrefPubMedGoogle Scholar
  • 12 Dusková M, Cermáková I, Hill M, Vanková M, Sámalíková P, Stárka L. What may be the markers of the male equivalent of polycystic ovary syndrome?. Physiol Res 2004; 53 (3) 287-294
    PubMedGoogle Scholar
  • 13 Ferriman D, Purdie AW. The inheritance of polycystic ovarian disease and a possible relationship to premature balding. Clin Endocrinol (Oxf) 1979; 11 (3) 291-300
    CrossrefPubMedGoogle Scholar
  • 14 Govind A, Obhrai MS, Clayton RN. Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families. J Clin Endocrinol Metab 1999; 84 (1) 38-43
    CrossrefPubMedGoogle Scholar
  • 15 Chen ZJ, Zhao H, He L , et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 2011; 43 (1) 55-59
    CrossrefPubMedGoogle Scholar
  • 16 Goodarzi MO, Jones MR, Li X , et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J Med Genet 2012; 49 (2) 90-95
    CrossrefPubMedGoogle Scholar
  • 17 Pau C, Saxena R, Welt CK. Evaluating reported candidate gene associations with polycystic ovary syndrome. Fertil Steril 2013; 99 (6) 1774-1778
    CrossrefPubMedGoogle Scholar
  • 18 Shi Y, Zhao H, Shi Y , et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet 2012; 44 (9) 1020-1025
    CrossrefPubMedGoogle Scholar
  • 19 Bailey T. Options for combination therapy in type 2 diabetes: comparison of the ADA/EASD position statement and AACE/ACE algorithm. Am J Med 2013; 126 (9) (Suppl. 01) S10-S20
    CrossrefPubMedGoogle Scholar
  • 20 Bennett W, Wilson L, Bolen S , et al. Oral Diabetes Medications for Adults with Type 2 Diabetes: An Update. USA: Agency for Healthcare Research and Quality; 2011. . Report No.: Comparative Effectiveness Review No. 27
    Google Scholar
  • 21 Kahn SE, Haffner SM, Heise MA , et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355 (23) 2427-2443
    CrossrefPubMedGoogle Scholar
  • 22 Kong WJ, Zhang H, Song DQ , et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism 2009; 58 (1) 109-119
    CrossrefPubMedGoogle Scholar
  • 23 Zhang H, Wei J, Xue R , et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 2010; 59 (2) 285-292
    CrossrefPubMedGoogle Scholar
  • 24 Zhou L, Yang Y, Wang X , et al. Berberine stimulates glucose transport through a mechanism distinct from insulin. Metabolism 2007; 56 (3) 405-412
    CrossrefPubMedGoogle Scholar
  • 25 Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008; 57 (5) 712-717
    CrossrefPubMedGoogle Scholar
  • 26 Balen AH, Rutherford AJ. Managing anovulatory infertility and polycystic ovary syndrome. BMJ 2007; 335 (7621) 663-666
    CrossrefPubMedGoogle Scholar
  • 27 Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43 (5) 647-654
    CrossrefPubMedGoogle Scholar
  • 28 Misso ML, Teede HJ, Hart R , et al. Status of clomiphene citrate and metformin for infertility in PCOS. Trends Endocrinol Metab 2012; 23 (10) 533-543
    CrossrefPubMedGoogle Scholar
  • 29 Bhagavath B, Carson SA. Ovulation induction in women with polycystic ovary syndrome: an update. Am J Obstet Gynecol 2012; 206 (3) 195-198
    CrossrefPubMedGoogle Scholar
  • 30 Legro RS, Barnhart HX, Schlaff WD , et al; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356 (6) 551-566
    CrossrefPubMedGoogle Scholar
  • 31 Morin-Papunen L, Rantala AS, Unkila-Kallio L , et al. Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab 2012; 97 (5) 1492-1500
    CrossrefPubMedGoogle Scholar
  • 32 Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2012; 5: CD003053
    Google Scholar
  • 33 Li Y, Kuang H, Shen W , et al. Letrozole, berberine, or their combination for anovulatory infertility in women with polycystic ovary syndrome: study design of a double-blind randomised controlled trial. BMJ Open 2013; 3 (11) e003934
    CrossrefPubMedGoogle Scholar
  • 34 Palomba S, Falbo A, La Sala GB. Metformin and gonadotropins for ovulation induction in patients with polycystic ovary syndrome: a systematic review with meta-analysis of randomized controlled trials. Reprod Biol Endocrinol 2014; 12 (1) 3
    CrossrefPubMedGoogle Scholar
  • 35 An Y, Sun Z, Zhang Y, Liu B, Guan Y, Lu M. The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment. Clin Endocrinol (Oxf) 2014; 80 (3) 425-431
    CrossrefPubMedGoogle Scholar
  • 36 Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010; 16 (4) 347-363
    CrossrefPubMedGoogle Scholar
  • 37 Pillay OC, Te Fong LF, Crow JC , et al. The association between polycystic ovaries and endometrial cancer. Hum Reprod 2006; 21 (4) 924-929
    PubMedGoogle Scholar
  • 38 Dokras A, Clifton S, Futterweit W, Wild R. Increased prevalence of anxiety symptoms in women with polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril 2012; 97 (1) 225 , e2
    CrossrefPubMedGoogle Scholar
  • 39 Deeks AA, Gibson-Helm ME, Paul E, Teede HJ. Is having polycystic ovary syndrome a predictor of poor psychological function including anxiety and depression?. Hum Reprod 2011; 26 (6) 1399-1407
    CrossrefPubMedGoogle Scholar
  • 40 Costello M, Shrestha B, Eden J, Sjoblom P, Johnson N. Insulin-sensitising drugs versus the combined oral contraceptive pill for hirsutism, acne and risk of diabetes, cardiovascular disease, and endometrial cancer in polycystic ovary syndrome. Cochrane Database Syst Rev 2007; (1) CD005552
    PubMedGoogle Scholar
  • 41 Bajuk Studen K, Jensterle Sever M, Pfeifer M. Cardiovascular risk and subclinical cardiovascular disease in polycystic ovary syndrome. Front Horm Res 2013; 40: 64-82
    PubMedGoogle Scholar
  • 42 Welt CK, Carmina E. Lifecycle of polycystic ovary syndrome (PCOS): from in utero to menopause. J Clin Endocrinol Metab 2013; 98 (12) 4629-4638
    CrossrefPubMedGoogle Scholar
  • 43 La Marca A, Artensio AC, Stabile G, Volpe A. Metformin treatment of PCOS during adolescence and the reproductive period. Eur J Obstet Gynecol Reprod Biol 2005; 121 (1) 3-7
    CrossrefPubMedGoogle Scholar
  • 44 Carmina E. PCOS: metabolic impact and long-term management. Minerva Ginecol 2012; 64 (6) 501-505
    PubMedGoogle Scholar
  • 45 Bohannon NJ. Individualized treatment of type 2 diabetes mellitus using noninsulin agents: clinical considerations for the primary care physician. Postgrad Med 2012; 124 (4) 95-108
    CrossrefPubMedGoogle Scholar
  • 46 Nicandri KF, Hoeger K. Diagnosis and treatment of polycystic ovarian syndrome in adolescents. Curr Opin Endocrinol Diabetes Obes 2012; 19 (6) 497-504
    CrossrefPubMedGoogle Scholar
  • 47 Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 2008; 93 (11) 4299-4306
    CrossrefPubMedGoogle Scholar
  • 48 Ibáñez L, Díaz M, Sebastiani G, Marcos MV, López-Bermejo A, de Zegher F. Oral contraception vs insulin sensitization for 18 months in nonobese adolescents with androgen excess: posttreatment differences in C-reactive protein, intima-media thickness, visceral adiposity, insulin sensitivity, and menstrual regularity. J Clin Endocrinol Metab 2013; 98 (5) E902-E907
    CrossrefPubMedGoogle Scholar
  • 49 Zhao Y, Qiao J. Ethnic differences in the phenotypic expression of polycystic ovary syndrome. Steroids 2013; 78 (8) 755-760
    CrossrefPubMedGoogle Scholar