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Polycystic Ovarian Syndrome(PCOs)
Polycystic Ovarian Syndrome is defined as endocrinologic diseases among reproductive-age women caused by undeveloped follicles clumping on the ovaries that interferes with the function of the normal ovaries associated with a high risk for metabolic disorder(1) as resulting of enlarged ovaries(2), leading to hormone imbalance(excessive androgen and anti-müllerian hormone (AMH) )(1)(3)(4)(5), induced Hirsutism(6)(7), reproductive disorder(10(12)), risks of type 2 diabetes(9)(10)(11), metabolic syndrome(10)(12) and early cardiovascular disease(8)(13), acne(10)(14), endometrial cancer(18)(19),weight gain and obesity(15)(16)(17). The syndrome effects over 5% of women population or 1 in 20 women.
Unfortunately, according to studies, women with PCOs after the reproductive age, are associated to continuously increase risk of type II diabetes, with no increasing altered glucose tolerance(20), CVD and hypertension(21).
The causes of polycystic ovarian syndrome are still unknown(69)(70), but there are some suggestions
1. Genetic predisposition
A genetic predisposition is defined as a genetic mutation of some women who were born predisposed to certain health problems(75). In this case, it is polycystic ovarian syndrome(70)(71)(72)(73)(74) .
2. Insulin resistance(82)
Insulin resistance is defined as abnormal levels of insulin in the blood of a person found to be associated to women with PCOs(83). It may be caused by certain health problems such as diabetes(76)(77), abnormal function of pancreas(78)(79) or caused low numbers of the insulin sensitivity of cells(79)(80), which impair the process of glucose in energy conversion(81), induced high blood glucose levels in the body, cause of increasing the risks of ovarian cysts development(83).
Obesity is defined as a person whose BMI index is over 24. As we known, obesity women in most cases are associated to clinical feature of insulin resistance(76). According to Università Cattolica del Sacro Cuore, low 25(OH)D levels(86) accompanied with the degree of adiposity may induce the causation of PCOs(85).
Hyperandrogenism is a medical condition characterized by excessive production and/or secretion of androgens leading to male pattern hair growth, probably due to mutation in the polymorphism rs12720071 in women(88). According to Erciyes University, there is a relation between IR(Insulin resistance) and androgenetic alopecia (AGA)(87), a male pattern baldness.
Hirsutism develops when follicles in androgen sensitive areas start to form thick, pigmented hair as opposed to thin, short, non-pigmented hair normally seen in those areas in women with PCOs(89). Evaluating terminal hair growth on the chin or lower abdomen may be a reliable source for predicting hirsutism, according to Ahvaz Jundishapur University of Medical Sciences(90).
5. Environmental chemicals
Environment chemicals endocrine disruptors(91)(92), such as such as xanoestrogen, and lifestyle(91)(92) can causes over production of certain hormone and reduction of others, leading to abnormal function of the reproductive organs including the development of follicles and increasing the risk of PCOs(93).
6. Food adulteration
Food adulteration, including mixing, substituting, concealing the quality of food by mislabeling, putting up decomposed or expired food, and adding toxic substances(94) can lead to hormone imbalance(98) and distort the natural process of women reproductive system(97) and in same cases, result in death(95)(96).
7. Chronic inflammation
Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells which are present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process(99)(100)(101).
8. Disorders of cortisol metabolism
Cortisol is usually referred to as the stress hormone, presented in high levels in patients with schizophrenia and bipolar disorder(104) as it is secreted in large volume for our body to response to stress and anxiety(103). Disorders of cortisol metabolism is defined as a condition of which cortisol hormone has lost its function in restoring glucose homeostasis(105) in balancing insulin and glucagon in the blood stream(107). According to University College London Hospitals, altered cortisol metabolism does not seem to be the primary cause of PCOS(102).
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(1) Adiposity and metabolic dysfunction in polycystic ovary syndrome by Sam S.(PubMed)
(2) A "kiss" before conception: triggering ovulation with kisspeptin-54 may improve IVF by Young SL.(PubMed)
(3.) Androgen hyperfunction and excessive heterosexual hair growth in women, with special attention to the polycystic ovarian syndrome by Lunde O1.(PubMed)
(4) Expression of anti-Müllerian hormone in letrozole rat model of polycystic ovary syndrome by Du DF1, Li XL, Fang F, Du MR.(PubMed)
(5) [Serum levels of anti-muller hormone in women with polycystic ovary syndrome and healthy women of reproductive age].[Article in Bulgarian] by Parahuleva N, Pehlivanov B, Orbecova M, Deneva T, Uchikova E.(PubMed)
(6) [Current opinions on the etiology and pathophysiology of hirsutism].[Article in Polish] by Krysiak R1, Kedzia A, Okopień B.(PubMed)
(7) The clinical evaluation of hirsutism by Somani N1, Harrison S, Bergfeld WF.(PubMed)
(8) Polycystic ovary syndrome and insulin: our understanding in the past, present and future by Mayer SB1, Evans WS, Nestler JE.(PubMed)
(9) Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome by Dogan BA1, Arduc A2, Tuna MM1, Karakılıc E1, Dagdelen I1, Tutuncu Y1, Berker D1, Guler S1.(PubMed)
(10) Approach to the patient: contraception in women with polycystic ovary syndrome by Yildiz BO1.(PubMed)
(11) Polycystic ovarian syndrome (PCOS): a significant contributor to the overall burden of type 2 diabetes in women by Talbott EO1, Zborowski JV, Rager JR, Kip KE, Xu X, Orchard TJ.(PubMed)
(12) Prevalence of vitamin D deficiency in Slovak women with polycystic ovary syndrome and its relation to metabolic and reproductive abnormalities by Figurová J1, Dravecká I, Javorský M, Petríková J, Lazúrová I.(PubMed)
(13) Role of Insulin Sensitizers on Cardiovascular Risk Factors in Polycystic Ovarian Syndrome: A Meta-Analysis by Thethi TK1, Katalenich B2, Nagireddy P3, Chabbra P4, Kuhadiya N5, Fonseca V1.(PubMed)
(14) Acne in hirsute women by Lumezi BG1, Pupovci HL1, Berisha VL1, Goçi AU2, Gerqari A3.(PubMed)
(15) Obesity and polycystic ovary syndrome by Naderpoor N1, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ.(PubMed)
(16) Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan by Teede H1, Deeks A, Moran L.(PubMed)
(17) Metabolic Evidence of Diminished Lipid Oxidation in Women WithPolycystic Ovary Syndrome. by Whigham LD1, Butz DE2, Dashti H3, Tonelli M3, Johnson LK1, Cook ME2, Porter WP4, Eghbalnia HR5, Markley JL6, Lindheim SR7, Schoeller DA8, Abbott DH9, Assadi-Porter FM10.(PubMed)
(18) Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis by Barry JA1, Azizia MM1, Hardiman PJ2.(PubMed)
(19) Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study by Gottschau M1, Kjaer SK2, Jensen A1, Munk C1, Mellemkjaer L3.(PubMed)
(20) Polycystic ovary syndrome: metabolic consequences and long-term management by Carmina E1.(PubMed)
(21) Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women with a polycystic ovary syndrome phenotype by Armeni E1, Stamatelopoulos K, Rizos D, Georgiopoulos G, Kazani M, Kazani A, Kolyviras A, Stellos K, Panoulis K, Alexandrou A, Creatsa M, Papamichael C, Lambrinoudaki I.(PubMed)
(65) [Association between levels of serum leptin and insulin resistance in patients with polycystic ovary syndrome].[Article in Chinese]by Cheng X1, Guo J2, Xie J3.(PubMed)
(66) [Clinical study on treating insulin resistance and promoting ovulation in polycystic ovary syndrome].[Article in Chinese]by Liu ZA1, Xue YM, Chen LX, Cai Q, Chen H, Zhang J, Cui QH, Ge J, Yuan T.(PubMed)
(67) Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome by Al-Zubeidi H, Klein KO.(PubMed)
(68) Randomized controlled trial evaluating response to metformin versus standard therapy in the treatment of adolescents with polycystic ovary syndrome by Allen HF1, Mazzoni C, Heptulla RA, Murray MA, Miller N, Koenigs L, Reiter EO.(PubMed)
(69) [Polycystic ovary syndrome: physiopathology review].[Article in Spanish]by Fux Otta C, Fiol de Cuneo M, Szafryk de Mereshian P.(PubMed)
(70) Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome by Batista MC1, Duarte Ede F2, Borba MD3, Zingler E4, Mangussi-Gomes J3, dos Santos BT5, de Moraes OL5, Hayashida SA6, Baracat EC6, da Rocha Neves Fde A5, Maciel GA6, Bachega TA7, Barra GB8, Lofrano-Porto A9.(PubMed)
(71) Polycystic ovary syndrome woman with heterozygous androgen receptor gene mutation who gave birth to a child with androgen insensitivity syndromeby Nam H1, Kim CH2, Cha MY1, Kim JM3, Kang BM1, Yoo HW3.(PubMed)
(72) The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS by Baculescu N1.(PubMed)
(73) Study on the zona pellucida 4 (ZP4) gene sequence and its expression in the ovaries of patients with polycystic ovary syndrome by Meczekalski B1, Nawrot R, Nowak W, Czyzyk A, Kedzia H, Gozdzicka-Jozefiak A.(PubMed)
(74) Association study of polymorphism of FXIIIVal34Leu gene andpolycystic ovary syndrome by Wang X1, Yang Y1, Huang Y2, Wang Q3.(PubMed)
(75) Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility by Roos-Araujo D1, Stuart S1, Lea RA1, Haupt LM1, Griffiths LR2.(PubMed)
(76) Mechanisms linking obesity to insulin resistance and type 2 diabetes by Kahn SE1, Hull RL, Utzschneider KM.(PubMed)
(77) The effect of past antibiotic exposure on diabetes risk by Boursi B1, Mamtani R2, Haynes K3, Yang YX4.(PubMed)
(78) Portal versus systemic venous drainage of the pancreatic graft: the effect on glucose metabolism in pancreas and kidney transplant recipients by Havrdova T1, Boucek P2, Jedinakova T2, Lipar K3, Kocik M3, Skibova J4, Saudek F2.(PubMed)
(79) The mechanisms linking adiposopathy to type 2 diabetes by Yang J1, Kang J, Guan Y.(PubMed)
(80) Caffeic acid, naringenin and quercetin enhance glucose-stimulatedinsulin secretion and glucose sensitivity in INS-1E cells by Bhattacharya S1, Oksbjerg N, Young JF, Jeppesen PB.(PubMed)
(81) Insulin resistance and adipogenesis: role of transcription and secreted factors by Penkov DN1, Egorov AD, Mozgovaya MN, Tkachuk VA.(PubMed)
(82) Insulin resistance in PCOS by Diamanti-Kandarakis E1(PubMed)
(83) Mouse models to study polycystic ovary syndrome: a possible link between metabolism and ovarian function? by van Houten EL1, Visser JA2.(PubMed)
(84)Epidemiologic investigation of polycystic ovarian syndrome (PCOS) in Han ethnic women of reproductive age in Liaoning Province, China by Jiao J, Fang Y, Wang T, Wang Z, Zhou M, Wang X.(PubMed)
(85) Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or acause-effect in PCOS?by Muscogiuri G1, Policola C, Prioletta A, Sorice G, Mezza T, Lassandro A, Della Casa S, Pontecorvi A, Giaccari A.(PubMed)
(86) Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome by Wehr E1, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, Obermayer-Pietsch B.(PubMed)
(87) The association of androgenetic alopecia and insulin resistance is independent of hyperandrogenemia: A case-control study by Kartal D1, Borlu M, Çınar SL, Ferahbaş A, Ulaş Y, Ünlühızarcı K, Ukşal Ü, Keleştimur F.(PubMed)
(88) GG genotype Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome by Jędrzejuk D1, Laczmański L, Kuliczkowska J, Lenarcik A, Trzmiel-Bira A, Hirnle L, Dorobisz U, Milewicz A, Lwow F, Urbanovych A, Słoka N.(PubMed)
(89) Women self-perception of excess hair growth, as a predictor of clinical hirsutism: a population-based study by Kazemi H1, Ramezani Tehrani F, Minooee S, Khalili D, Azizi F.(PubMed)
(90) Evaluation of only the chin or lower abdomen for predicting hirsutism by Rashidi H1, Parizi ZT, Mohammadi M.(PubMed)
(91) The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS) by Mick Rae, Cathal Grace, Kirsten Hogg, Lisa Marie Wilson, Sophie L. McHaffie,2 Seshadri Ramaswamy, Janis MacCallum, Fiona Connolly, Alan S. McNeilly,and Colin Duncan (PubMed)
(92) Prenatal androgen exposure leads to alterations in gene and protein expression in the ovine fetal ovary by Hogg K1, McNeilly AS, Duncan WC.(PubMed)
(93) Endocrine-Disrupting Chemicals: Some Actions of POPs on Female Reproduction by Ewa L. Gregoraszczuk* and Anna Ptak(PubMed)
(94) Food Adulteration and Consumer Awareness in Dhaka City, 1995-2011 By Sharifa Nasreencorresponding author1 and Tahmeed Ahmed(PubMed)
(95) FAO/WHO. Assuring food safety and quality: guidelines for strengthening national food control systems. Rome: Food and Agriculture Organization; 2003. p. 28. (FAO food and nutrition paper no. 76).
(96) Park K. Park's textbook of preventive and social medicine. 18th ed. Jabalpur: Banarsidas Bhanot; 2005. p. 481.
(97) Menstrual effects among women exposed to polychlorinated biphenyls and dibenzofurans by Yang CY1, Huang TS, Lin KC, Kuo P, Tsai PC, Guo YL.(PubMed)
(98) Endocrine modulators in the food chain and environment by Nilsson R1.(PubMed)
(99) Adipose tissue dysfunction, adipokines and low-grade chronicinflammation in PCOS by Spritzer PM1, Lecke SB2, Satler F3, Morsch DM4.(PubMed)
(100) Adipose tissue dysfunction in polycystic ovary syndrome by Villa J1, Pratley RE.(PubMed)
(101) Adipose tissue, metabolic syndrome and polycystic ovary syndrome: from pathophysiology to treatment by Garruti G1, Depalo R, Vita MG, Lorusso F, Giampetruzzi F, Damato AB, Giorgino F.(PubMed)
(102) Altered cortisol metabolism in polycystic ovary syndrome: insulin enhances 5alpha-reduction but not the elevated adrenal steroid production rates by Tsilchorozidou T1, Honour JW, Conway GS.(PubMed)
(103) Increased testosterone levels and cortisol awakening responses in patients with borderline personality disorder: Gender and trait aggressiveness matter by Rausch J1, Gäbel A1, Nagy K1, Kleindienst N2, Herpertz SC1, Bertsch K3.(PubMed|)
(104) Increased systemic cortisol metabolism in patients with schizophrenia and bipolar disorder: a mechanism for increased stress vulnerability? by Steen NE1, Methlie P, Lorentzen S, Hope S, Barrett EA, Larsson S, Mork E, Almås B, Løvås K, Agartz I, Melle I, Berg JP, Andreassen OA.(PubMed)
(105) Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy by Keller-Wood M1, Feng X2, Wood CE3, Richards E2, Anthony RV4, Dahl GE5, Tao S5.(PubMed)
(106) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man by Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.(PubMed)
(107) Glucose Homeostasis and Starvation(Glucose Homeostasis)