The Different Phenotypes of Polycystic Ovary Syndrome: No Advantages for Identifying Women with Aggravated Insulin Resistance or Impaired Lipids

Abstract

Background: According to the classification of polycystic ovary syndrome (PCOS) published by the Androgen Excess Society (AES), 10 different phenotypes of the condition are possible. The question remains of whether using these phenotypes might enable us to identify women with impaired insulin resistance or an impaired lipid profile among patients with PCOS.

Materials and Methods: A prospective cohort analysis was performed of 313 women with diagnosed PCOS and 80 control individuals. The screening panel included a physical examination, weight and height measurement, ultrasonography of the ovaries, and hormone, glucose, lipid, and insulin resistance measurements.

Results: There were no statistically significant differences in insulin resistance parameters between the different phenotypes. There were no statistically significant differences in body mass index (BMI) in any of the groups, but BMI showed the best correlation with insulin resistance in all women with PCOS and controls. Sex hormone-binding globulin (SHBG) was inversely correlated with insulin resistance in women with PCOS and controls. High-density lipoprotein (HDL) was negatively correlated with insulin resistance, and free testosterone was positively correlated with it, only in women with PCOS.

Conclusions: Using the different phenotypes described in the AES classification shows no advantages for identifying women with aggravated insulin resistance or impaired lipid profile among patients with PCOS.

Key words

PCOS - insulin resistance - lipid profile - androgen parameters

References

• 1 Anon. . Economic consequences of diabetes mellitus in the U.S. in 1997 . American Diabetes Association.  Diabetes Care. 1998;  21 296-309 DOI: doi: 10.2337/diacare.21.2.296
• 2 Alberti KG. The costs of non-insulin-dependent diabetes mellitus.  Diabet Med. 1997;  14 7-9
• 3 Amato MC, Galluzzo A, Finocchiaro S. et al . The evaluation of metabolic parameters and insulin sensitivity for a more robust diagnosis of the polycystic ovary syndrome.  Clin Endocrinol. 2008;  69 52-60
• 4 Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome.  Best Pract Res Clin Obstet Gynaecol. 2004;  18 737-754
• 5 Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature.  J Clin Endocrinol Metab. 2006;  91 781-785
• 6 Azziz R, Carmina E, Dewailly D. et al . Androgen Excess Society. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline.  J Clin Endocrinol Metab. 2006;  91 4237-4245
• 7 Chereau A. Mémoires pour servir à l’étude des maladies des ovaires.. Paris: Fortin, Masson; 1844
• 8 Cupisti S, Dittrich R, Binder H. et al . Influence of body mass index on calculated androgen parameters in adult women with hirsutism and PCOS.  Exp Clin Endocrinol Diabetes. 2007a;  115 380-386
• 9 Cupisti S, Dittrich R, Binder H. et al . Evaluation of biochemical hyperandrogenemia and body mass index in women presenting with amenorrhea.  Exp Clin Endocrinol Diabetes. 2007b;  115 298-302
• 10 Cupisti S, Kajaia N, Dittrich R. et al . Body mass index and ovarian function are associated with endocrine and metabolic abnormalities in women with hyperandrogenic syndrome.  Eur J Endocrinol. 2008;  158 711-719
• 11 Cupisti S, Giltay EJ, Gooren LJ. et al . The impact of testosterone administration to female-to-male transsexuals on insulin resistance and lipid parameters compared with women with polycystic ovary syndrome.  Fertil Steril. 2010a;  94 2647-2653
• 12 Cupisti S, Haeberle L, Dittrich R. et al . Smoking is associated with increased free testosterone and fasting insulin levels in women with polycystic ovary syndrome, resulting in aggravated insulin resistance.  Fertil Steril. 2010b;  94 673-677
• 13 Dittrich R, Kajaia N, Cupisti S. et al . Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS.  Reprod Biomed Online. 2009;  19 319-325
• 14 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis.  Endocr Rev. 1997;  18 774-800
• 15 Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome.  Lancet. 2005;  365 1415-1428
• 16 Fruzzetti F, Perini D, Lazzarini V. et al . Adolescent girls with polycystic ovary syndrome showing different phenotypes have a different metabolic profile associated with increasing androgen levels.  Fertil Steril. 2009;  92 626-634
• 17 Geisthovel F, Rabe T. The ESHRE/ASRM consensus on polycystic ovary syndrome (PCOS) – an extended critical analysis.  Reprod Biomed Online. 2007;  14 522-535
• 18 Geisthövel F, Wacker A, Brabant G. et al . Novel systematics of nomenclature and classification of female functional androgenization (including polycystic ovary syndrome and non-classic congenital adrenal hyperplasia).  J Reproduktionsmed Endokrinol. 2010;  7 6-26
• 19 Isomaa B, Almgren P, Tuomi T. et al . Cardiovascular morbidity and mortality associated with the metabolic syndrome.  Diabetes Care. 2001;  24 683-689
• 20 Kajaia N, Binder H, Dittrich R. et al . Low sex hormone-binding globulin as a predictive marker for insulin resistance in women with hyperandrogenic syndrome.  Eur J Endocrinol. 2007;  157 499-507
• 21 Mathur RS, Moody LO, Landgrebbe S. et al . Plasma androgens and sex hormone binding globulin in the evaluation of hirsute patients.  Fertil Steril. 1981;  35 29-37
• 22 Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.  Diabetes Care. 1999;  22 1462-1470
• 23 Matthews DR, Hosker JP, Rudenski AS. et al . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
• 24 Meigs JB, Wilson PW, Fox CS. et al . Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease.  J Clin Endocrinol Metab. 2006;  91 2906-2912
• 25 Meigs JB, Rutter MK, Sullivan LM. et al . Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome.  Diabetes Care. 2007;  30 1219-1225
• 26 Mueller A, Dittrich A, Cupisti S. et al . Is it necessary to measure free testosterone to assess hyperandrogenemia in women? The role of calculated free and bioavailable testosterone.  Exp Clin Endocrinol Diabetes. 2006a;  114 182-187
• 27 Mueller A, Cupisti S, Binder H. et al . The role of albumin in the calculation of free and bioavailable testosterone in women with hyperandrogenemia.  In Vivo. 2006b;  20 403-407
• 28 Mueller A, Cupisti S, Binder H. et al . Endocrinological markers for assessment of hyperandrogenemia in hirsute women.  Horm Res. 2007a;  67 35-41
• 29 Mueller A, Kiesewetter F, Binder H. et al . Long-term administration of testosterone undecanoate every 3 months for testosterone supplementation in female-to-male transsexuals.  J Clin Endocrinol Metab. 2007b;  92 3470-3475
• 30 Mueller A, Gooren LJ, Naton-Schötz S. et al . Prevalence of polycystic ovary syndrome (PCOS) and hyperandrogenemia in female-to-male transsexuals.  J Clin Endocrinol Metab. 2008;  93 1408-1411
• 31 Mueller A, Schöfl C, Dittrich R. et al . Thyroid-stimulating hormone is associated with insulin resistance independently of body mass index and age in women with polycystic ovary syndrome.  Hum Reprod. 2009;  24 2924-2930
• 32 Norman RJ, Dewailly D, Legro RS. et al . Polycystic ovary syndrome.  Lancet. 2007;  370 685-697
• 33 Oppelt PG, Mueller A, Jentsch K. et al . The effect of metformin treatment for 2 years without caloric restriction on endocrine and metabolic parameters in women with polycystic ovary syndrome.  Exp Clin Endocrinol Diabetes. 2010;  118 633-637
• 34 Ovalle F, Azziz R. Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus.  Fertil Steril. 2002;  77 1095-1105
• 35 Radikova Z, Koska J, Huckova M. et al . Insulin sensitivity indices: a proposal of cut-off points for simple identification of insulin-resistant subjects.  Exp Clin Endocrinol Diabetes. 2006;  114 249-256
• 36 Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
• 37 Rokitansky C. A manual of pathological anatomy, vol. 2 [trans. by Edward Sieveking from original German edition of 1844].. Philadelphia: Blanchard, Lea; 1855: 246
• 38 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.  Fertil Steril. 2004a;  81 19-25
• 39 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).  Hum Reprod. 2004b;  19 41-47
• 40 Shroff R, Syrop CH, Davis W. et al . Risk of metabolic complications in the new PCOS phenotype based on the Rotterdam criteria.  Fertil Steril. 2007;  88 1389-1395
• 41 Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries.  Am J Obstet Gynecol. 1935;  29 181-191
• 42 Vermeulen A, Verdonck L, Kaufmann JM. A critical evaluation of simple methods for the estimation of free testosterone in serum.  J Clin Endocrinol Metab. 1999;  84 3666-3672
• 43 Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach.. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, eds. Polycystic ovary syndrome Boston: Blackwell Scientific; 1992: 377-384

Correspondence