Free Testosterone Level Correlated with the Metabolic Abnormalities Dependent on Central Obesity in Women with Polycystic Ovary Syndrome

Abstract

Background:

Women with polycystic ovary syndrome (PCOS) have increased risks of developing metabolic abnormalities compared with the women without PCOS. Hyperandrogenemia is one of the most important characteristics of PCOS. However, the correlations between hyperandrogenemia and metabolic disorders are uncertain.

Aim:

To elucidate the relationship between androgen indices and metabolic abnormalities in Chinese women with PCOS.

Subjects and Methods:

A retrospective analysis of the anthropometric and biochemical records of 408 women with PCOS.

Results:

The prevalence of metabolic syndrome (MetS) was 15.7% in women with PCOS. No association existed between total testosterone (TT) and metabolic profile. Free testosterone (FT) correlated with most of the metabolic variables by unadjusted correlation analyses. The women with elevated FT levels exhibited more unfavorable metabolic profiles compared with the women with normal FT levels. After adjusting for the confounding factors by multivariate logistic regression analysis, the women with elevated FT levels had higher prevalence of central obesity than the women with normal FT levels (odds ratio [OR] 2.346, p=0.042). Women with reduced sex hormone-binding globulin levels were more likely to have central obesity, overweight, raised fasting glucose, insulin resistance, and raised diastolic blood pressure. Raised dehydroepiandrosterone sulfate (DHEAS) level was associated with a lower probability of having central obesity (OR 0.293, p=0.001) and overweight (OR 0.47, p=0.023).

Conclusions:

FT has closer association with metabolic parameters than TT. FT can involve in the development of metabolic disorders dependent on central obesity. Raised DHEAS level can reduce the risks of central obesity and overweight.

Key words

polycystic ovary syndrome - androgens - free testosterone - metabolic abnormalities - central obesity

• References

• 1 March WA, Moore VM, Willson KJ et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010; 25: 544-551
• 2 Ni RM, Mo Y, Chen X et al. Low prevalence of the metabolic syndrome but high occurrence of various metabolic disorders in Chinese women with polycystic ovary syndrome. Eur J Endocrinol 2009; 161: 411-418
• 3 Cussons AJ, Watts GF, Burke V et al. Cardiometabolic risk in polycystic ovary syndrome: a comparison of different approaches to defining the metabolic syndrome. Hum Reprod 2008; 23: 2352-2358
• 4 Moran LJ, Misso ML, Wild RA et al. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010; 16: 347-363
• 5 Wild RA, Carmina E, Diamanti-Kandarakis E et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010; 95: 2038-2049
• 6 Barber TM, Wass JA, McCarthy MI et al. Metabolic characteristics of women with polycystic ovaries and oligo-amenorrhoea but normal androgen levels: implications for the management of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007; 66: 513-517
• 7 Shroff R, Syrop CH, Davis W et al. Risk of metabolic complications in the new PCOS phenotypes based on the Rotterdam criteria. Fertil Steril 2007; 88: 1389-1395
• 8 Diamanti-Kandarakis E, Panidis D. Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS. Clin Endocrinol (Oxf) 2007; 67: 735-742
• 9 Lindholm A, Andersson L, Eliasson M et al. Prevalence of symptoms associated with polycystic ovary syndrome. Int J Gynaecol Obstet 2008; 102: 39-43
• 10 Coviello AD, Legro RS, Dunaif A. Adolescent girls with polycystic ovary syndrome have an increased risk of the metabolic syndrome associated with increasing androgen levels independent of obesity and insulin resistance. J Clin Endocrinol Metab 2006; 91: 492-497
• 11 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
• 12 Rossi B, Sukalich S, Droz J et al. Prevalence of metabolic syndrome and related characteristics in obese adolescents with and without polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93: 4780-4786
• 13 Cagnacci A, Paoletti AM, Arangino S et al. Effect of ovarian suppression on glucose metabolism of young lean women with and without ovarian hyperandrogenism. Hum Reprod 1999; 14: 893-897
• 14 Krotkiewski M, Landin K, Dahlgren E et al. Effect of two modes of antiandrogen treatment on insulin sensitivity and serum leptin in women with PCOS. Gynecol Obstet Invest 2003; 55: 88-95
• 15 Dahlgren E, Landin K, Krotkiewski M et al. Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome. Hum Reprod 1998; 13: 2706-2711
• 16 Elkind-Hirsch KE, Valdes CT, Malinak LR. Insulin resistance improves in hyperandrogenic women treated with Lupron. Fertil Steril 1993; 60: 634-641
• 17 Carmina E, Chu MC, Longo RA et al. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab 2005; 90: 2545-2549
• 18 Falhammar H, Filipsson H, Holmdahl G et al. Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2007; 92: 110-116
• 19 Alberti KG, Zimmet P, Shaw J. Metabolic syndrome – a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med 2006; 23: 469-480
• 20 Chen X, Ni R, Mo Y et al. Appropriate BMI levels for PCOS patients in Southern China. Hum Reprod 2010; 25: 1295-1302
• 21 Standards of medical care in diabetes – 2009. Diabetes Care 2009; 32: S13-S61
• 22 Chen X, Yang D, Li L et al. Abnormal glucose tolerance in Chinese women with polycystic ovary syndrome. Hum Reprod 2006; 21: 2027-2032
• 23 Kuk JL, Lee S, Heymsfield SB et al. Waist circumference and abdominal adipose tissue distribution: influence of age and sex. Am J Clin Nutr 2005; 81: 1330-1334
• 24 Godoy-Matos AF, Vaisman F, Pedrosa AP et al. Central-to-peripheral fat ratio, but not peripheral body fat, is related to insulin resistance and androgen markers in polycystic ovary syndrome. Gynecol Endocrinol 2009; 25: 793-798
• 25 Despres JP, Moorjani S, Lupien PJ et al. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 1990; 10: 497-511
• 26 Nestler JE, Powers LP, Matt DW et al. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991; 72: 83-89
• 27 Heald AH, Anderson SG, Ivison F et al. Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups. Exp Clin Endocrinol Diabetes 2005; 113: 522-528
• 28 Wild RA, Painter PC, Coulson PB et al. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985; 61: 946-951
• 29 Chen MJ, Yang WS, Yang JH et al. Low sex hormone-binding globulin is associated with low high-density lipoprotein cholesterol and metabolic syndrome in women with PCOS. Hum Reprod 2006; 21: 2266-2271
• 30 Selva DM, Hogeveen KN, Innis SM et al. Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. J Clin Invest 2007; 117: 3979-3987
• 31 Anderson DC. Sex-hormone-binding globulin. Clin Endocrinol (Oxf) 1974; 3: 69-96
• 32 Nishizawa H, Shimomura I, Kishida K et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 2002; 51: 2734-2741
• 33 Luukkaa V, Pesonen U, Huhtaniemi I et al. Inverse correlation between serum testosterone and leptin in men. J Clin Endocrinol Metab 1998; 83: 3243-3246
• 34 Chen MJ, Chen CD, Yang JH et al. High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and a reduced risk of abdominal obesity in women with polycystic ovary syndrome. Hum Reprod 2011; 26: 227-234
• 35 Kauffman RP, Baker VM, DiMarino P et al. Hyperinsulinemia and circulating dehydroepiandrosterone sulfate in white and Mexican American women with polycystic ovary syndrome. Fertil Steril 2006; 85: 1010-1016
• 36 Brennan K, Huang A, Azziz R. Dehydroepiandrosterone sulfate and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril 2009; 91: 1848-1852
• 37 Carmina E, Lobo RA. Prevalence and metabolic characteristics of adrenal androgen excess in hyperandrogenic women with different phenotypes. J Endocrinol Invest 2007; 30: 111-116
• 38 Marcondes JA, Hayashida SA, Barcellos CR et al. Metabolic syndrome in women with polycystic ovary syndrome: prevalence, characteristics and predictors. Arq Bras Endocrinol Metabol 2007; 51: 972-979
• 39 Rittmaster RS, Deshwal N, Lehman L. The role of adrenal hyperandrogenism, insulin resistance, and obesity in the pathogenesis of polycystic ovarian syndrome. J Clin Endocrinol Metab 1993; 76: 1295-1300
• 40 Jakubowicz DJ, Beer NA, Beer RM et al. Disparate effects of weight reduction by diet on serum dehydroepiandrosterone-sulfate levels in obese men and women. J Clin Endocrinol Metab 1995; 80: 3373-3376
• 41 Wild RA, Umstot ES, Andersen RN et al. Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism. Am J Obstet Gynecol 1983; 146: 602-606
• 42 Barrett-Connor E, Ferrara A. Dehydroepiandrosterone, dehydroepiandrosterone sulfate, obesity, waist-hip ratio, and noninsulin-dependent diabetes in postmenopausal women: the Rancho Bernardo Study. J Clin Endocrinol Metab 1996; 81: 59-64
• 43 Kumar A, Woods KS, Bartolucci AA et al. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2005; 62: 644-649
• 44 Moran C, Knochenhauer E, Boots LR et al. Adrenal androgen excess in hyperandrogenism: relation to age and body mass. Fertil Steril 1999; 71: 671-674
• 45 Orentreich N, Brind JL, Rizer RL et al. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab 1984; 59: 551-555
• 46 Rasmusson AM, Wu R, Paliwal P et al. A decrease in the plasma DHEA to cortisol ratio during smoking abstinence may predict relapse: a preliminary study. Psychopharmacology (Berl) 2006; 186: 473-480