Citation Information :
Chauhan V, Kumari S. Polycystic Ovary Syndrome Till Date and Possibilities in Coming Years. J South Asian Feder Obs Gynae 2024; 16 (2):169-173.
Polycystic ovary disease and syndrome are the less understood entities affecting the structure of the ovaries and thereby leading to various metabolic diseases. Here, an insight into the pathophysiology of polycystic ovarian syndrome (PCOS) and biochemical and genetical alteration is discussed based on the various researches held in last years. Impaired biosynthesis of the specific steroidogenic enzymes causing hormonal imbalances are yet to be studied. Exposure of the androgen in female offsprings leading to insulin resistance in adulthood seen in multiple animal studies needs to be proved in humans too. Animal studies have shown that nerve growth factor is associated with the sympathetic nervous system and raised in the PCOS also contributing to raised levels of catecholamine. The role of Kit Ligand intraovarian cytokine KL signaling and its regulation in human ovaries is to be cleared. More studies like impact of weight reduction, the use of oral contraceptive treatment reduces androgens in PCOS female. Also the role of insulin sensitizers is to be studied in the management of adolescents with PCOS. Polycystic ovarian syndrome demands a broad experimental approach from its identification to treatment. New ‘omic’ technologies are needed to be utilized to identify the responsible genes/proteins or molecules to treat this disease. It is better to identify the women with PCOS and preventing them against the type 2 diabetes, cardiovascular diseases, and few hormone-dependent cancers. While more human studies are to be done for a long time on small and large scales to identify the causing factors, risk-reducing factors, treatment and prediction of the other comorbidities or cancers in future due to PCOS.
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 2004;19(1):41–47. DOI: https://doi.org/10.1093/humrep/deh098.
Escobar-Morreale HF, Botella-Carretero JI, Alvarez-Blasco F, et al. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery. J Clin Endocrinol Metab 2005;90(12)6364–6369. DOI: 10.1210/jc.2005-1490.
Longcope C. Adrenal and gonadal androgen secretion in normal females. Clin Endocrinol Metab 1986;15(2):213–228. DOI: 10.1016/s0300-595x(86)80021-4.
Bardin CW, Lipsett MB. Testosterone and androstenedione blood production rates in normal women and women with idiopathic hirsutism or polycystic ovaries. J Clin Invest 1967;46(5):891–902. DOI: 10.1172/JCI105588.
Rosner W, Auchus RJ, Azziz R, et al. Utility, limitations, and pitfalls in measuring testosterone: An endocrine society position statement. J Clin Endocrinol Metab 2007;92(2):405–413. DOI: 10.1210/jc. 2006-1864.
Stener-Victorin E, Holm G, Labrie F, et al. Are there any sensitive and specific sex steroid markers for polycystic ovary syndrome? J Clin Endocrinol Metab 2010;95(5):810–819. DOI: 10.1210/jc.2009-1908.
Piltonen T, Koivunen R, Morin-Papunen L, et al. Ovarian and adrenal steroid production: Regulatory role of LH/HCG. Hum Reprod 2002;17(3):620–624. DOI: 10.1093/humrep/17.3.620.
Lasley BL, Santoro N, Randolf JF, et al. The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity. J Clin Endocrinol Metab 2002;87(8):3760–3767. DOI: 10.1210/jcem.87.8.8741.
Piltonen T, Koivunen R, Ruokonen A, et al. Ovarian age-related responsiveness to human chorionic gonadotropin. J Clin Endocrinol Metab 2003;88(7):3327–3332. DOI: 10.1210/jc.2002-021549.
Puurunen J, Piltonen T, Jaakkola P, et al. Adrenal androgen production capacity remains high up to menopause in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2009;94(6),1973–1978. DOI: 10.1210/jc.2008-2583.
Draper N, Powell BL, Franks S, et al. Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome. Clinical Endocrinol (Oxf) 2006;65:64–70. DOI: 10.1111/j.1365-2265.2006.02547.x.
Stewart PM, Shackleton CH, Beastall GH, et al. 5 alpha-reductase activity in polycystic ovary syndrome. Lancet 1990;335(8687): 431–433. DOI: 10.1016/0140-6736(90)90664-q.
Gambineri A, Forlani G, Munarini A, et al. Increased clearance of cortisol by 5beta-reductase in a subgroup of women with adrenal hyperandrogenism in polycystic ovary syndrome. J Endocrinol Invest 2009;32(3):210–218. DOI: 10.1007/BF03346454.
Rodin A, Thakkar H, Taylor N, et al. Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11 beta-hydroxysteroid dehydrogenase. 1994;330(7):460–465. DOI: 10.1056/NEJM199402173300703.
Dissen GA, Garcia-Ruda C, Paredes A, et al. Excessive ovarian production of nerve growth factor facilitates development of cystic ovarian morphology in mice and is a feature of polycystic ovarian syndrome in humans. Endocrinology 2009;150(6):2906–2914. DOI: 10.1210/en.2008-1575.
Fagius J. Sympathetic nerve activity in metabolic control – some basic concepts. Acta Physiol Scand 2003;177(3):337–343. DOI: 10.1046/j.1365-201X.2003.01086.x.
Heider U, Pedal I, Spanel-Borowski K. Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries. Fertil Steril 2001;75(6):1141–1147. DOI: https://doi.org/10.1016/S0015-0282(01) 01805-2.
Giallauria F, Palomba S, Manguso F, et al. Abnormal heart rate recovery after maximal cardiopulmonary exercise stress testing in young overweight women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2008;68(1):88–93. DOI: 10.1111/j.1365-2265.2007.03004.x.
Tekin G, Tekin A, Kilicarslan EB, et al. Altered autonomic neural control of the cardiovascular system in patients with polycystic ovary syndrome. Int J Cardiol 2008;130(1):49–55. DOI: 10.1016/j.ijcard.2007.08.037.
Yildirir A, Aybar F, Kabakci G, et al. Heart rate variability in young women with polycystic ovary syndrome. Ann Noninvasive Electrocardiol 2006;11(4):306–312. DOI: 10.1111/j.1542-474X.2006.00122.x.
Sverrisdottir YB, Mogren T, Kataoka J, et al. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab 2008;294(3):E576–E581. DOI: 10.1152/ajpendo.00725.2007.
Willis D, Mason H, Gilling-Smith C, et al. Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab 1996;81(1):302–309. DOI: 10.1210/jcem.81.1.8550768.
Rice S, Pellatt L, Ramanathan K, et al. Metformin inhibits aromatase via an extracellular signal-regulated kinase-mediated pathway. Endocrinology 2009;150(10):4794–4801. DOI: 10.1210/en.2009- 0540.
Elting MW, Kwee J, Korsen TJ, et al. Aging women with polycystic ovary syndrome who achieve regular menstrual cycles have a smaller follicle cohort than those who continue to have irregular cycles. Fertil Steril 2003;79(5):1154–1160. DOI: 10.1016/s0015-0282(03)00152-3.
Willis DS, Watson H, Mason HD, et al. Premature response to luteinizing hormone of granulosa cells from anovulatory women with polycystic ovary syndrome: Relevance to mechanism of anovulation. J Clin Endocrinol Metab 1998;83(11):3984–3991. DOI: 10.1210/jcem.83.11.5232.
Balen AH, Conway GS, Kaltsas G, et al. Polycystic ovary syndrome: The spectrum of the disorder in 1741 patients. Hum Reprod 1995;10(8):2107–2111. DOI: 10.1093/oxfordjournals.humrep.a136243.
Pigny P, Merlen E, Robert Y, et al. Elevated serum level of anti-mullerian hormone in patients with polycystic ovary syndrome: Relationship to the ovarian follicle excess and to the follicular arrest. J Clin Endocrinol Metab 2003;88(12):5957–5962. DOI: 10.1210/jc.2003-030727.
Mulders AG, Laven JS, Eijkemans MJ, et al. Changes in anti-Mullerian hormone serum concentrations over time suggest delayed ovarian ageing in normogonadotrophic anovulatory infertility. Hum Reprod 2004;19(9):2036–2042. DOI: 10.1093/humrep/deh37.
Schachter M, Balen AH, Patel A, et al. Hypogonadotropic patients with ultrasonographically detected polycystic ovaries: Endocrine response to pulsatile gonadotropin-releasing hormone. Gynecol Endocrinol 1996;10(5):327–335. DOI: 10.3109/09513599609012819.
Balen AH, Laven JS, Tan SL, et al. Ultrasound assessment of the polycystic ovary: International consensus definitions. Hum Reprod 2003;9(6):505–514. DOI: 10.1093/humupd/dmg044.
Nagamani M, Hannigan EV, Dinh TV, et al. Hyperinsulinemia and stromal luteinization of the ovaries in postmenopausal women with endometrial cancer. J Clin Endocrinol Metab 1988;67(1):144–148. DOI: 10.1210/jcem-67-1-144.
Pascale MM, Pugeat M, Roberts M, et al. Androgen suppressive effect of GnRH agonist in ovarian hyperthecosis and virilizing tumours. Clin Endocrinol (Oxf) 1994;41(5):571–576. DOI: 10.1111/j.1365-2265.1994.tb01820.x.
Abbott DH, Tarantal AF, Dumesic DA. Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. Am J Primatol 2009;71(9): 776–784. DOI: 10.1002/ajp.20679.
Abbott DH, Barnett DK, Levine JE, et al. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod 2008;79(1):154–163. DOI: 10.1095/biolreprod.108.067702.
Anderson H, Fogel N, Grebe SK, et al. Infants of women with polycystic ovary syndrome have lower cord blood androstenedione and estradiol levels. J Clin Endocrinol Metab 2010;95(5):2180–2186. DOI: 10.1210/jc.2009-2651.
Fernandez-Real JM, Lopez-Bermejo A, Vendrell J, et al. Burden of infection and insulin resistance in healthy middle-aged men. Diabetes Care 2006;29(5):1058–1064. DOI: 10.2337/diacare.2951058.
Sabuncu T, Vural H, Harma M, et al. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease. Clin Biochem 2001;34(5):407–413. DOI: 10.1016/s0009-9120(01) 00245-4.
Orio Jr F, Palomba S, Cascella T, et al. The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90(1):2–5. DOI: 10.1210/jc.2004-0628.
McCartney CR, Blank SK, Prendergast KA, et al. Obesity and sex steroid changes across puberty: Evidence for marked hyperandrogenemia in pre- and early pubertal obese girls. J Clin Endocrinol Metab 2007;92(2):430–436. DOI: 10.1210/jc.2006-2002.
Reinehr T, de Sousa G, Roth CL, et al. Androgens before and after weight loss in obese children. J Clin Endocrinol Metab 2005;90(10):5588–5595. DOI: 10.1210/jc.2005-0438.
Hoeger K, Davidson K, Kochman L, et al. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 2008;93(11): 4299–4306. DOI: 10.1210/jc.2008-0461.
Diamanti-Kandarakis E, Katsikis I, Piperi C, et al. Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2008;69(4):634–641. DOI: 10.1111/j.1365-2265.2008.03247.x.
Diamanti-Kandarakis E, Katsikis I, Piperi C, et al. Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2007;66(1):103–109. DOI: 10.1111/j.1365-2265.2006.02693.x.
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(5):946–951. DOI: 10.1210/jcem-61-5-946.
Talbott E, Clerici A, Berga SL, et al. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: Results of a case–control study. J Clin Epidemiol 1998;51(5):415–422. DOI: 10.1016/s0895-4356(98)00010-9.
Ehrmann DA, Liljenquist DR, Kasza K, et al. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91(1):48–53. DOI: 10.1210/jc.2005-1329.
Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001;111(8):607–613. DOI: 10.1016/s0002-9343(01)00948-2.
Graf MJ, Richards CJ, Brown V, et al. The independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein profiles in women. Clin Endocrinol (Oxf) 1990;33(1): 119–131. DOI: 10.1111/j.1365-2265.1990.tb00472.x.
Shaw LJ, Bairey Merz CN, Reis SE, et al. Ischemic heart disease in women: Insights from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Part I: Sex differences in traditional and novel risk factors, symptom evaluation and gender-optimized diagnostic strategies. J Am Coll Cardiol 2006;47(3 Suppl):S4–S20. DOI: 10.1016/j.jacc.2005.01.072.
Pierpoint T, McKeigue PM, Isaacs AJ, et al. Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 1998;51(7):581–586. DOI: 10.1016/s0895-4356(98)00035-3.
Legro RS. Polycystic ovary syndrome and cardiovascular disease: A pre- mature association? Endocrinol Rev 2003;24(3):302–312. DOI: 10.1210/er.2003-0004.
Abbott DH, Zhou R, Bird IM, et al. Fetal programming of adrenal androgen excess: Lessons from a nonhuman primate model of polycystic ovary syndrome. Endocr Dev 2008;13:145–158. DOI: 10.1159/000134831.
Mohamed-Hussein ZA, Harun S. Construction of a polycystic ovarian syndrome (PCOS) pathway based on the interactions of PCOS-related proteins retrieved from bibliomic data. Theor Biol Med Model 2009;6:18. DOI: 10.1186/1742-4682-6-18.