An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome

References

• Azziz R, Carmina E, Sawaya ME. Idiopathic hirsutism. Endocr Rev 2000;21:347–362.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Hermann AP, Hagen C, Jensen LT, Frystyk J, Bennett P, Flyvbjerg A, Andersen M. A randomized placebo-controlled study on the effects of pioglitazone on cortisol metabolism in polycystic ovary syndrome. Fertil Steril 2009;91(3):842–850.
   PubMed Web of Science ®Google Scholar
• Azziz R, Carmina E, Dewailly D, Amanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91:456–488.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Henriksen JE, Andersen M, Hagen C, Hangaard J, Rasmussen P, et al The prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian, premenopausal women with hirsutism as primary diagnosis. Fertil Steril 2004;82:1570–1579.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Andersen M, Richelsen B, Bruun JM. Plasma monocyte chemo-attractant protein-1 and macrophage inflammatory protein-1α are increased in patients with polycystic ovary syndrome and associated with adiposity, but unaffected by pioglitazone treatment. Clin Endocrinol (Oxf) 2009 Jan 19. Epub ahead of print.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Hermann AP, Brusgaard K, Hangaard J, Hagen C, Andersen M. Significantly higher adrenocorticotropin-stimulated cortisol and 17-hydroxyprogesterone levels in 337 consecutive, premenopausal, caucasian, hirsute patients compared with healthy controls. J Clin Endocrinol Metab 2005;90:1347–1353.
   PubMed Web of Science ®Google Scholar
• Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19–25.
   PubMed Web of Science ®Google Scholar
• Ehrmann DA, Rosenfield RL, Barnes RB, Brigell DF, Sheikh Z. Detection of functional ovarian hyperandrogenism in women with androgen excess. N Engl J Med 1992;327:157–162.
   PubMed Web of Science ®Google Scholar
• Azziz R, Black VY, Knochenhauer ES, Hines GA, Boots LR. Ovulation after glucocorticoid suppression of adrenal androgens in the polycystic ovary syndrome is not predicted by the basal dehydroepiandrosterone sulfate level. J Clin Endocrinol Metab 1999;84:946–950.
   PubMed Web of Science ®Google Scholar
• Garcia-Rudaz MC, Ropelato MG, Escobar ME, Veldhuis JD, Barontini M. Augmented frequency and mass of LH discharged per burst are accompanied by marked disorderliness of LH secretion in adolescents with polycystic ovary syndrome. Eur J Endocrinol 1998;139:621–630.
   PubMed Web of Science ®Google Scholar
• Balen AH. Hypersecretion of luteinizing hormone and the polycystic ovary syndrome. Hum Reprod 1993;8(Suppl 2):123–128.
   PubMedGoogle Scholar
• Gilling-Smith C, Story H, Rogers V, Franks S. Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Clin Endocrinol (Oxf) 1997;47:93–99.
   PubMed Web of Science ®Google Scholar
• Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996;335:617–623.
   PubMed Web of Science ®Google Scholar
• Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, d-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003;(3): CD003053.
   Google Scholar
• Mathur R, Alexander CJ, Yano J, Trivax B, Azziz R. Use of metformin in polycystic ovary syndrome. Am J Obstet Gynecol 2008;199:596–609.
   PubMed Web of Science ®Google Scholar
• Palomba S, Falbo A, Zullo F, Orio F, Jr. Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev 2009;30:1–50.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Hermann AP, Andersen M, Hagen C, Beck-Nielsen H, Veldhuis JD, Henriksen JE. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome. Fertil Steril 2006;86:385–397.
   PubMed Web of Science ®Google Scholar
• Barnes RB, Rosenfield RL, Burstein S, Ehrmann DA. Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N Engl J Med 1989;320:559–565.
   PubMed Web of Science ®Google Scholar
• Kumar A, Woods KS, Bartolucci AA, Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2005;62:644–649.
   PubMed Web of Science ®Google Scholar
• Zhang LH, Rodriguez H, Ohno S, Miller WL. Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc Natl Acad Sci USA 1995;92:10619–10623.
   PubMed Web of Science ®Google Scholar
• Kauffman RP, Baker VM, DiMarino P, Castracane VD. Hyperinsulinemia and circulating dehydroepiandrosterone sulfate in white and Mexican American women with polycystic ovary syndrome. Fertil Steril 2006;85:1010–1016.
   PubMed Web of Science ®Google Scholar
• Stewart PM, Shackleton CH, Beastall GH, Edwards CR. 5α-reductase activity in polycystic ovary syndrome. Lancet 1990;335:431–433.
   PubMed Web of Science ®Google Scholar
• Tsilchorozidou T, Honour JW, Conway GS. Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5α-reduction but not the elevated adrenal steroid production rates. J Clin Endocrinol Metab 2003;88:5907–5913.
   PubMed Web of Science ®Google Scholar
• Ibanez L, DiMartino-Nardi J, Potau N, Saenger P. Premature adrenarche – normal variant or forerunner of adult disease? Endocr Rev 2000;21:671–696.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Hojlund K, Andersen NR, Hansen BF, Beck-Nielsen H, Wojtaszewski JF. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment. J Clin Endocrinol Metab 2008;93:3618–3626.
   PubMed Web of Science ®Google Scholar
• Hojlund K, Glintborg D, Andersen NR, Birk JB, Treebak JT, Frosig C, Beck-Nielsen H, Wojtaszewski JF. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment. Diabetes 2008;57:357–366.
   PubMed Web of Science ®Google Scholar
• Bremer AA, Miller WL. The serine phosphorylation hypothesis of polycystic ovary syndrome: a unifying mechanism for hyperandrogenemia and insulin resistance. Fertil Steril 2008;89:1039–1048.
   PubMed Web of Science ®Google Scholar
• Bjorntorp P. The android woman – a risky condition. J Intern Med 1996;239:105–110.
   PubMed Web of Science ®Google Scholar
• Holmang A, Bjorntorp P. [Hyperandrogenism or insulin resistance. What is the cause and effect in diabetes among women?]. Lakartidningen 1993;90:4313–4315.
   PubMedGoogle Scholar
• Dunaif A, Green G, Futterweit W, Dobrjansky A. Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1990;70:699–704.
   PubMed Web of Science ®Google Scholar
• Pasquali R, Gambineri A, Anconetani B, Vicennati V, Colitta D, Caramelli E, et al The natural history of the metabolic syndrome in young women with the polycystic ovary syndrome and the effect of long-term oestrogen-progestagen treatment. Clin Endocrinol (Oxf) 1999;50:517–527.
   PubMed Web of Science ®Google Scholar
• Moran LJ, Noakes M, Clifton PM, Wittert GA, Tomlinson L, Galletly C, et al Ghrelin and measures of satiety are altered in polycystic ovary syndrome but not differentially affected by diet composition. J Clin Endocrinol Metab 2004;89:3337–3344.
   PubMed Web of Science ®Google Scholar
• Morgan J, Scholtz S, Lacey H, Conway G. The prevalence of eating disorders in women with facial hirsutism: an epidemiological cohort study. Int J Eat Disord 2008;41:427–431.
   PubMed Web of Science ®Google Scholar
• Moran LJ, Noakes M, Clifton PM, Wittert GA, Le Roux CW, Ghatei MA, Bloom SR, Norman RJ. Postprandial ghrelin, cholecystokinin, peptide YY, and appetite before and after weight loss in overweight women with and without polycystic ovary syndrome. Am J Clin Nutr 2007;86:1603–1610.
   PubMed Web of Science ®Google Scholar
• Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril 2008 Dec 3. Epub ahead of print.
   Google Scholar
• Escobar-Morreale HF, Botella-Carretero JI, varez-Blasco F, Sancho J, San Millan JL. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery. J Clin Endocrinol Metab 2005;90:6364–6369.
   PubMed Web of Science ®Google Scholar
• Rasmussen MH, Hvidberg A, Juul A, Main KM, Gotfredsen A, Skakkebaek NE, et al Massive weight loss restores 24-hour growth hormone release profiles and serum insulin-like growth factor-I levels in obese subjects. J Clin Endocrinol Metab 1995;80:1407–1415.
   PubMed Web of Science ®Google Scholar
• Lanzone A, Villa P, Fulghesu AM, Pavone V, Caruso A, Mancuso S. The growth hormone response to growth hormone-releasing hormone is blunted in polycystic ovary syndrome: relationship with obesity and hyperinsulinaemia. Hum Reprod 1995;10:1653–1657.
   PubMed Web of Science ®Google Scholar
• Cordido F, Peino R, Penalva A, Alvarez CV, Casanueva FF, Dieguez C. Impaired growth hormone secretion in obese subjects is partially reversed by acipimox-mediated plasma free fatty acid depression. J Clin Endocrinol Metab 1996;81:914–918.
   PubMed Web of Science ®Google Scholar
• Kopelman PG. Hormones and obesity. Baillieres Clin Endocrinol Metab 1994;8:549–575.
   PubMedGoogle Scholar
• Glintborg D, Stoving RK, Hagen C, Hermann AP, Frystyk J, Veldhuis JD, Flyvbjerg A, Andersen A. Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:5605–5612.
   PubMed Web of Science ®Google Scholar
• Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte chemo-attractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab 2005;90:2282–2289.
   PubMed Web of Science ®Google Scholar
• Banaszewska B, Pawelczyk L, Spaczynski RZ, Dziura J, Duleba AJ. Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial. J Clin Endocrinol Metab 2007;92:456–461.
   PubMed Web of Science ®Google Scholar
• Ibanez L, Jaramillo AM, Ferrer A, de Zegher F. High neutrophil count in girls and women with hyperinsulinaemic hyperandrogenism: normalization with metformin and flutamide overcomes the aggravation by oral contraception. Hum Reprod 2005;20:2457–2462.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Andersen M, Hagen C, Frystyk J, Hulstrom V, Flyvbjerg A, Hermann AP. Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls. Eur J Endocrinol 2006;155:337–345.
   PubMed Web of Science ®Google Scholar
• Ardawi MS, Rouzi AA. Plasma adiponectin and insulin resistance in women with polycystic ovary syndrome. Fertil Steril 2005;83:1708–1716.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Frystyk J, Hojlund K, Andersen KK, Henriksen JE, Hermann AP, et al Total and high molecular weight (HMW) adiponectin levels and measures of glucose and lipid metabolism following pioglitazone treatment in a randomized placebo-controlled study in polycystic ovary syndrome. Clin Endocrinol (Oxf) 2008;68:165–174.
   PubMed Web of Science ®Google Scholar
• Pagotto U, Gambineri A, Vicennati V, Heiman ML, Tschop M, Pasquali R. Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels. J Clin Endocrinol Metab 2002;87:5625–5629.
   PubMed Web of Science ®Google Scholar
• Barber TM, Casanueva FF, Karpe F, Lage M, Franks S, McCarthy MI, et al Ghrelin levels are suppressed and show a blunted response to oral glucose in women with polycystic ovary syndrome. Eur J Endocrinol 2008;158:511–516.
   PubMed Web of Science ®Google Scholar
• Carmina E, Ferin M, Gonzalez F, Lobo RA. Evidence that insulin and androgens may participate in the regulation of serum leptin levels in women. Fertil Steril 1999;72:926–931.
   PubMed Web of Science ®Google Scholar
• Bornstein SR, Rutkowski H, Vrezas I. Cytokines and steroidogenesis. Mol Cell Endocrinol 2004;215:135–141.
   PubMed Web of Science ®Google Scholar
• Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA, Chrousos GP. Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 2007;18:280–285.
   PubMed Web of Science ®Google Scholar
• Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992;71:599–604.
   PubMed Web of Science ®Google Scholar
• Pirwany IR, Fleming R, Greer IA, Packard CJ, Sattar N. Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters. Clin Endocrinol (Oxf) 2001;54:447–453.
   PubMed Web of Science ®Google Scholar
• Macut D, Damjanovic S, Panidis D, Spanos N, Glisic B, Petakov M, et al Oxidised low-density lipoprotein concentration – early marker of an altered lipid metabolism in young women with PCOS. Eur J Endocrinol 2006;155:131–136.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Hojlund K, Andersen M, Henriksen JE, Beck-Nielsen H, Handberg A. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment. Diabetes Care 2008;31:328–334.
   PubMed Web of Science ®Google Scholar
• Handberg A, Levin K, Hojlund K, Beck-Nielsen H. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance. Circulation 2006;114:1169–1176.
   PubMed Web of Science ®Google Scholar
• Yeh ET, Anderson HV, Pasceri V, Willerson JT. C-reactive protein: linking inflammation to cardiovascular complications. Circulation 2001;104:974–975.
   PubMed Web of Science ®Google Scholar
• Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141–146.
   PubMed Web of Science ®Google Scholar
• Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Position statement: glucose intolerance in polycystic ovary syndrome a position statement of the androgen excess society. J Clin Endocrinol Metab 2007;92:4546–4556.
   PubMed Web of Science ®Google Scholar
• Boudreaux MY, Talbott EO, Kip KE, Brooks MM, Witchel SF. Risk of T2DM and impaired fasting glucose among PCOS subjects: results of an 8-year follow-up. Curr Diab Rep 2006;6:77–83.
   PubMedGoogle Scholar
• Norman RJ, Masters L, Milner CR, Wang JX, Davies MJ. Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome. Hum Reprod 2001;16:1995–1998.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Andersen M, Hagen C, Hermann AP. Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism. Clin Endocrinol (Oxf) 2005;62:683–691.
   PubMed Web of Science ®Google Scholar
• Yuksel O, Dokmetas HS, Topcu S, Erselcan T, Sencan M. Relationship between bone mineral density and insulin resistance in polycystic ovary syndrome. J Bone Miner Metab 2001;19:257–262.
   PubMed Web of Science ®Google Scholar
• Rejnmark L. Bone effects of glitazones and other anti-diabetic drugs. Curr Drug Saf 2008;3:194–198.
   PubMedGoogle Scholar
• Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, et al Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427–2443.
   PubMed Web of Science ®Google Scholar
• Glintborg D, Andersen M, Hagen C, Heickendorff L, Hermann AP. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial. J Clin Endocrinol Metab 2008;93:1696–1701.
   PubMed Web of Science ®Google Scholar
• Xita N, Georgiou I, Tsatsoulis A. The genetic basis of polycystic ovary syndrome. Eur J Endocrinol 2002;147:717–725.
   PubMed Web of Science ®Google Scholar
• Escobar-Morreale HF, Luque-Ramirez M, San Millan JL. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev 2005;26:251–282.
   PubMed Web of Science ®Google Scholar
• Goodarzi MO. Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med 2008;26:5–13.
   PubMed Web of Science ®Google Scholar
• Ibanez L, Potau N, Marcos MV, de Zegher F. Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 1999;84:4739–4741.
   PubMed Web of Science ®Google Scholar
• Francois I, de Zegher F. Adrenarche and fetal growth. Pediatr Res 1997;41:440–442.
   PubMed Web of Science ®Google Scholar
• Laitinen J, Taponen S, Martikainen H, Pouta A, Millwood I, Hartikainen AL, Roukonen A, Sovio U, McCarthy MI, Franks S, et al Body size from birth to adulthood as a predictor of self-reported polycystic ovary syndrome symptoms. Int J Obes Relat Metab Disord 2003;27:710–715.
   PubMed Web of Science ®Google Scholar
• Dumesic DA, Abbott DH, Padmanabhan V. Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord 2007;8:127–141.
   PubMed Web of Science ®Google Scholar
• Gitau R, Adams D, Fisk NM, Glover V. Fetal plasma testosterone correlates positively with cortisol. Arch Dis Child Fetal Neonatal Ed 2005;90:F166–F169.
   Web of Science ®Google Scholar
• Stikkelbroeck NM, Hermus AR, Braat DD, Otten BJ. Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Obstet Gynecol Surv 2003;58:275–284.
   PubMed Web of Science ®Google Scholar
• Kuijper EA, Vink JM, Lambalk CB, Boomsma DI. Prevalence of polycystic ovary syndrome in women from opposite-sex twin pairs. J Clin Endocrinol Metab 2009;94:1987–1990.
   PubMed Web of Science ®Google Scholar
• Li Z, Huang H. Epigenetic abnormality: a possible mechanism underlying the fetal origin of polycystic ovary syndrome. Med Hypotheses 2008;70:638–642.
   PubMed Web of Science ®Google Scholar