Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Should Subclinical Hypothyroidism Be an Exclusion Criterion for the Diagnosis of Polycystic Ovary Syndrome?

Authors
1 Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
2 Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil
3 University of Adelaide, Robinson Research Institute and Fertility SA, Adelaide, Australia
Abstract
Background: The purpose of the study was to examine whether patients with subclinical hypothyroidism (SCH) should be excluded before making a diagnosis of polycystic ovary syndrome (PCOS). Methods: Seven hundred sixteen patients, 462 with true PCOS, 31 with PCOS-SCH, and 223 normal cycling women were enrolled. Clinical, metabolic, and hormonal parameters among the groups were investigated. Continuous variables were compared by one-way analysis of variance. Proportions were compared using Z test. Fisher test was used to compare categorical variables. Simple correlation was performed using Spearman’s coefficient. Correlation between thyroid stimulating hormone (TSH) and dependent variables were performed using backward multiple regression. The significance level was set at 0.05. Results: True polycystic ovary and polycystic ovary with subclinical hypothyroidism patients presented similar anthropometrical parameters. C-peptide was higher in polycystic ovary patients than in the other groups (p=0.014). Prevalence of glucose intolerance (p=0.186) and insulin resistance (p=0.293) was not statistically different in polycystic ovary and polycystic ovary with subclinical hypothyroidism. TSH levels showed positive correlation with lean body mass (p=0.032), total cholesterol (p=0.046, insulin (p=0.048) and prolactin (p=0.047). Backward multiple regression model retained TC, insulin, and PRL as predictors of TSH levels (p=0.011). Conclusion: Anthropometric parameters and ovary morphology were similar in both PCOS and PCOS-with-SCH patients. Regarding hormones, only C-peptide was higher in PCOS group. TSH correlated with total cholesterol, insulin, and prolactin. Before PCOS diagnosis, the exclusion criterion thyroid dysfunction should be standardized and subclinical hypothyroidism should not exclude a diagnosis of PCOS.
Keywords

  1. Kousta E, White DM, Cela E, McCarthy MI, Franks S. The prevalence of polycystic ovaries in women with infertility. Hum Reprod. 1999;14(11):2720-3.
  2. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544-51.
  3. 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. 2004;81(1):19-25.
  4. Pasquali R, Patton L, Pagotto U, Gambineri A. Metabolic alterations and cardiovascular risk factors in the polycystic ovary syndrome. Minerva Ginecol. 2005;57(1):79-85.
  5. Krassas GE, Pontikides N, Kaltsas T, Papadopoulou P, Paunkovic J, Paunkovic N, et al. Disturbances of menstruation in hypothyroidism. Clin Endocrinol (Oxf). 1999;50(5):655-9.
  6. Ghosh S, Kabir SN, Pakrashi A, Chatterjee S, Chakravarty B. Subclinical hypothyroidism: a determinant of polycystic ovary syndrome. Horm Res. 1993;39(1-2):61-6.
  7. Mueller A, Schöfl C, Dittrich R, Cupisti S, Oppelt PG, Schild RL, 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(11):2924-30.
  8. Maratou E, Hadjidakis DJ, Kollias A, Tsegka K, Peppa M, Alevizaki M, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160(5):785-90.
  9. Sridhar GR, Nagamani G. Hypothyroidism presenting with polycystic ovary syndrome. J Assoc Physicians India. 1993;41(2):88-90.
  10. Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87(2):489-99.
  11. Billic-Komarica E, Beciragic A, Junuzovic D. The Importance of HbA1c Control in Patients with Subclinical Hypothyroidism. Mater Sociomed. 2012;24(4):212-9.
  12. Kvetny J, Heldgaard PE, Bladbjerg EM, Gram J. Subclinical hypothyroidism is associated with a low-grade inflammation, increased triglyceride levels and predicts cardiovascular disease in males below 50 years. Clin Endocrinol (Oxf). 2004;61(2):232-8.
  13. Althaus BU, Staub JJ, Ryff-De Lèche A, Oberhänsli A, Stähelin HB. LDL/HDL-changes in subclinical hypothyroidism: possible risk factors for coronary heart disease. Clin Endocrinol (Oxf). 1988;28(2):157-63.
  14. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-9.
  15. Huang A, Brennan K, Azziz R. Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institutes of Health 1990 criteria. Fertil Steril. 2010;93(6):1938-41.
  16. Welt CK, Gudmundsson JA, Arason G, Adams J, Palsdottir H, Gudlaugsdottir G, et al. Characterizing discrete subsets of polycystic ovary syndrome as defined by the Rotterdam criteria: the impact of weight on phenotype and metabolic features. J Clin Endocrinol Metab. 2006;91(12):4842-8.
  17. Carmina E, Rosato F, Jannì A, Rizzo M, Longo RA. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab. 2006;91(1):2-6.
  18. Dittrich R, Kajaia N, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS. Reprod Biomed Online. 2009;19(3):319-25.
  19. Enzevaei A, Salehpour S, Third M, Saharkhiz N. Subclinical hypothyroidism and insulin resistance in polycystic ovary syndrome: is there a relationship? Iran J Reprod Med. 2014;12(7):481-6.
  20. Rotondi M, Cappelli C, Magri F, Botta R, Dionisio R, Iacobello C, et al. Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome. Clin Endocrinol (Oxf). 2011;75(3):378-81.
  21. Ganie MA, Laway BA, Wani TA, Zargar MA, Nisar S, Ahamed F, et al. Association of subclinical hypothyroidism and phenotype, insulin resistance, and lipid parameters in young women with polycystic ovary syndrome. Fertil Steril. 2011;95(6):2039-43.
  22. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003;13(1):3-126.
  23. DHSS/MRC Group on Obesity Research, Waterlow JC, James WPT, Great Britain, Department of Health and Social Security and Medical Research Council. Research on obesity: A repot of the DHSS/MRC group. Hher Majesty’s Stationary office, London; 1976. 94 p.
  24. Valdez R. A simple model-based index of abdominal adiposity. J Clin Epidemiol. 1991;44(9):955-6.
  25. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502.
  26. American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care. 2013;36 Suppl 1:S11-66.
  27. McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temple LA, et al. Diagnosing insulin resistance in the general population. Diabetes Care. 2001;24(3):460-4.
  28. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9.
  29. de Medeiros SF, Gil-Junior AB, Barbosa JS, Isaías ED, Yamamoto MM. New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary syndrome patients. Arq Bras Endocrinol Metabol. 2013;57(6):437-44.
  30. Wild RA, Vesely S, Beebe L, Whitsett T, Owen W. Ferriman Gallwey self-scoring I: performance assessment in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;90(7):4112-4.
  31. Lujan ME, Chizen DR, Pierson RA. Diagnostic criteria for polycystic ovary syndrome: pitfalls and controversies. J Obstet Gynaecol Can. 2008;30(8):671-9.
  32. Benetti-Pinto CL, Berini Piccolo VR, Garmes HM, Teatin Juliato CR. Subclinical hypothyroidism in young women with polycystic ovary syndrome: an analysis of clinical, hormonal, and metabolic parameters. Fertil Steril. 2013;99(2):588-92.
  33. Pei YJ, Wang AM, Zhao Y, Yan L, Li M, White RE, et al. Studies of cardiovascular risk factors in polycystic ovary syndrome patients combined with subclinical hypothyroidism. Gynecol Endocrinol. 2014;30(8):553-6.
  34. Huang R, Zheng J, Li S, Tao T, Liu W. Subclinical hypothyroidism in patients with polycystic ovary syndrome: distribution and its association with lipid profiles. Eur J Obstet Gynecol Reprod Biol. 2014;177:52-6.
  35. Garelli S, Masiero S, Plebani M, Chen S, Furmaniak J, Armanini D, et al. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;169(2):248-51.
  36. Janssen OE, Mehlmauer N, Hahn S, Offner AH, Gärtner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol. 2004;150(3):363-9.
  37. Celik C, Abali R, Tasdemir N, Guzel S, Yuksel A, Aksu E, et al. Is subclinical hypothyroidism contributing dyslipidemia and insulin resistance in women with polycystic ovary syndrome? Gynecol Endocrinol. 2012;28(8):615-8.
  38. Brenta G, Berg G, Arias P, Zago V, Schnitman M, Muzzio ML, et al. Lipoprotein alterations, hepatic lipase activity, and insulin sensitivity in subclinical hypothyroidism: response to L-T(4) treatment. Thyroid. 2007;17(5):453-60.
  39. Velija-Asimi Z. The role of subclinical hypothyroidism and vitamin D deficiency in the development of menstrual disorders in women with PCOS. In: Reincke M, Amara F, Chang CC, Deal Ch, Dunaif A, Ito H, et al, editors. European Congress of Endocrinology. 15th International & 14th European Congress of Endocrinology; 2012 May 5-9; Florence, Italy: Bioscientifica; p 916.