Abstract
PCOS patients are typically characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries, and these aspects are frequent in a high percentage of women during the reproductive life. PCOS frequently show overweight and/or obesity and are characterized by a higher production of androgens and reduced sensitivity to insulin. In fact it is of great importance to note that more than 40–45% of all PCOS patients show overweight up to obesity and that these patients have a modest up to an exaggerated hyperinsulinism in response to the standard oral glucose tolerance test (OGTT). What is relevant to point out is that such reduced insulin sensitivity can be observed also in 10–15% of the normal weight PCOS, thus confirming that hyperinsulinism can show up not only in relation to obesity or to excess of fat tissue but also as an intrinsic abnormal ability to control glucose metabolism.
Recent data clearly demonstrated that reduced insulin sensitivity can be gained with a specific attention to lifestyle, including not only a diet but also certain degree of physical activity. However, a specific effect on hyperinsulinemia can be achieved using glucose sensitizer drugs, such as metformin, so that to reduce the negative modulation exerted by hyperinsulinemia on the reproductive axis as well as on neuroendocrine control of reproduction with relevant effects also on adrenal function and neurosteroid production.
The evolution of therapeutical approach to PCOS proposed in recent years the use of inositol in two of the isomers at present available, that is myo-inositol (MYO) and D-chiro-inositol (DCI). These two compounds are tightly linked one to the other since MYO is transformed by an epimerase in DCI, having each tissue its own conversion rate, likely due to the specific needs for the two different molecules. In general both these compounds work as specific modulators of the intracellular second messenger activated by the insulin linkage with its own membrane receptor.
Recent data demonstrated also that integrative administration of MYO in lean PCOS ameliorated insulin response to OGTT and that both MYO and DCI reduced insulin response to OGTT in overweight or obese PCOS. Both isomers have been demonstrated to improve also ovarian function and LH response to GnRH stimulation, typically abnormal in PCOS patients. Though impossible to state what of the two isomers play the main role, it appears clear that the metabolic impairment(s) are great part of the casual factor(s) of the abnormal reproductive function in PCOS.
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References
Carmina E, Lobo RA (1999) Polycystic ovary syndrome: arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab 84:1897–1899
Zborowski JV, Cauley JA, Talbott EO et al (2000) Bone mineral density, androgens, and the polycystic ovary: the complex and controversial issue of androgenic influence in female bone. J Clin Endocrinol Metab 85:3496–3506
Zawadzki JK, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR (eds) Polycystic ovary syndrome. Blackwell, Boston, MA, pp 337–384
Polson DW, Adams J, Wadsworth J, Franks S (1988) Polycystic ovaries-a common finding in normal women. Lancet 1:870–872
Azziz R, Carmina E, Dewailly D, Androgen Excess Society et al (2006) Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 91:4237–4245
Palomba S, Falbo A, Zullo F, Orio F (2009) Evidence-based and potential benefits of metformin in the polycystic ovary syndrome: a comprehensive review. Endocr Rev 30:1–50
Deligeoroglou E, Kouskouti C, Christopoulos P (2009) The role of genes in the polycystic ovary syndrome: predisposition and mechanism. Gynecol Endocrinol 25:603–609
Hirschberg AL (2009) Polycystic ovary syndrome, obesity and reproductive implications. Womens Health 5:529–540
Genazzani AD, Petraglia F, Pianazzi F, Volpogni C, Genazzani AR (1993) The concomitant release of androstenedione with cortisol and luteinizing hormone pulsatile releases distinguishes adrenal from ovarian hyperandrogenism. Gynecol Endocrinol 7:33–41
Vrbikova J, Hainer V (2009) Obesity and polycystic ovary syndrome. Obes Facts 2:26–35
Chittenden BG, Fullerton G, Maheshwari A, Bhattacharya S (2009) Polycystic ovary syndrome and the risk of gynaecological cancer: a systematic review. Reprod Biomed Online 19:398–405
Nelson VL, Qin KN, Rosenfield RL et al (2001) The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab 86:5925–5933
Plouffe L Jr (2000) Disorders of excessive hair growth in the adolescent. Obstet Gynecol Clin North Am 27:79–99
Dunaif A, Green G, Futterweit W, Dobrjansky A (1990) Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in polycystic ovary syndrome J. Clin Endocrinol Metab 70:699–704
Barbieri RL (1990) The role of adipose tissue and hyperinsulinemia in the development of hyperandrogenism in women. In: Frisch RE (ed) Adipose tissue and reproduction. Karger, Basal, pp 42–57
Conway GS, Jacobs HS, Holly JM, Wass JA (1990) Effects of LH, insulin, insulin-like growth factor I and insulin-like growth factor small binding protein I in the polycystic ovary syndrome. Clin Endocrinol (Oxf) 33:593–603
Dunaif A, Givens JR, Haseltine F et al (1992) The polycystic ovary syndrome. Blackwell, Boston, MA
Mattsson LA, Gullberg G, Hamberger L, Samsioe G, Silverstolpe G (1984) Lipid metabolism in women with polycystic ovary syndrome: possible implications for an increased risk of coronary heart disease. Fertil Steril 42:579–584
Muniyappa R, Montagnani M, Koh KK, Quon MJ (2007) Cardiovascular actions of insulin. Endocr Rev 28:463–491
Carmina E (2009) Cardiovascular risk and events in polycystic ovary syndrome. Climacteric 12(Suppl 1):22–25
Eckel RH, Alberti KG, Grundy SM, Zimmet PZ (2010) The metabolic syndrome. Lancet 375(9710):181–183
Cornier MA, Dabelea D, Hernandez TL et al (2008) The metabolic syndrome. Endocr Rev 29:777–822
International Diabetes Federation (2006) The International Diabetes Federation consensus worldwide definition of the metabolic syndrome. http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf
Gluek CJ, Papanna R, Wang P (2003) Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 52:908–915
Apridonidze T, Essah PA, Iuorno MJ (2005) Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 90:1929–1935
Dockras A, Bochner M, Holinrake E (2005) Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol 106:131–137
Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB (1985) Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 61:946–951
Talbott EO, Guzick DS, Sutton-Tyrrell K, McHughPemu KP, Zborowski JV, Remsberg KE (2000) Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 20:2414–2421
Luscher TF, Richard V, Tshudi M, Yang ZH, Boulanger C (1990) Endothelial control of vascular tone in large and small coronary arteries. J Am Coll Cardiol 15:519–527
Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC (1990) Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 81:491–497
Legro RS (2003) Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr Rev 24:302–312
Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J (1999) Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 22:141–146
Palomba S, Russo T, Orio F Jr et al (2006) Uterine effects of metformin administration in anovulatory women with polycystic ovary syndrome. Hum Reprod 21:457–465
Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implication for pathogenesis. Endocr Rev 18:774–800
Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ (1994) Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 43:647–654
Tang T, Glanville J, Hayden CJ et al (2006) Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study. Hum Reprod 21:80–89
Knowler WC, Barrett-Connor E, Fowler SE, Diabetes Prevention Program Research Group et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403
Kitabchi AE, Temprosa M, Knowler WC et al (2005) Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Diabetes 54:2404–2414
Palomba S, Falbo A, Orio F, Zullo F (2008) Insulin sensitizing agents and reproductive function in polycystic ovary syndrome patients. Curr Opin Obstet Gynecol 20:364–373
Hsueh AJ, Billig H, Tsafriri A (1994) Ovarian follicle atresia: a hormonally controlled apoptotic process. Endocr Rev 15:707–724
Nieuwenhuis-Ruifrok AE, Kuchenbecker WK, Hoek A, Middleton P, Norman RJ (2009) Insulin sensitizing drugs or weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis. Hum Reprod Update 15:57–68
Genazzani AD, Battaglia C, Malavasi B, Strucchi C, Tortolani F, Gamba O (2004) Metformin dministration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome. Fertil Steril 81:114–119
Genazzani AD, Lanzoni C, Ricchieri F, Baraldi E, Casarosa E, Jasonni VM (2007) Metformin administration is more effective when non-obese patients with polycystic ovary syndrome show both hyperandrogenism and hyperinsulinemia. Gynecol Endocrinol 23:146–152
La Marca A, Morgante G, Paglia T, Ciotta L, Cianci A, De Leo V (1999) Effects of metformin on adrenal steroidogenesis in women with polycystic ovary syndrome. Fertil Steril 72:985–989
Patel K, Coffler MS, Dahan MH et al (2003) Increased luteinizing hormone secretion in women with polycystic ovary syndrome is unaltered by prolonged insulin infusion. J Clin Endocrinol Metab 88:5456–5461
Cosma M, Swiglo BA, Flynn DN et al (2008) Insulin sensitizers for the treatment of hirsutism: a systematic review and metaanalyses of randomized controlled trials. J Clin Endocrinol Metab 93:1135–1142
Budak E, Fernández Sánchez M, Bellver J, Cerveró A, Simón C, Pellicer A (2006) Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3–36 with the reproductive system. Fertil Steril 85:1563–1581
Saltiel AR (1990) Second messengers of insulin action. Diabetes Care 13:244–256
Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G (1999) Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 340:1314–1320
Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM (2008) Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 24:139–144
Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE, Apridonidze T, Iuorno MJ, Nestler JE (2006) Altered D-Chiro-Inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 29:300–305
Baillargeon JP, Iuorno MJ, Jakubowicz DJ, Apridonidze T, He N, Nestler JE (2004) Metformin therapy increases insulin-stimulated release of D-chiroinositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab 89:242–249
Genazzani AD, Ricchieri F, Prati A, Santagni S, Chierchia E, Rattighieri E, Campedelli A, Simoncini T, Artini PG (2012) Differential insulin response to myo-inositol administration in obese PCOS patients. Gynecol Endocrinol 28:969–973
Galazis N, Galazi M, Atiomo W (2011) D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol 27:256–262
Larner J (2002) D-chiro-Inositol—its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 3:47–60
Harwood K, Vuguin P, DiMartino-Nardi J (2007) Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. Horm Res 68:209–217
Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, Nestler JE (2002) Effects of D-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 8:417–423
Gerli S, Mignosa M, Di Renzo GC (2003) Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 7:151–159
Chiu TTY, Rogers MS, Law ELK, Briton-Jones CM, Cheung LP, Haines CJ (2002) Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 6:1591–1596
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Genazzani, A.D., Prati, A., Despini, G., Marini, G., Ricchieri, F. (2014). PCOS from Lifestyle to the Use of Inositol and Insulin Sensitizers. In: Genazzani, A.R., Brincat, M. (eds) Frontiers in Gynecological Endocrinology. ISGE Series. Springer, Cham. https://doi.org/10.1007/978-3-319-03494-2_7
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DOI: https://doi.org/10.1007/978-3-319-03494-2_7
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