The Holistic prevention, management and treatment of Polycystic Ovarian Syndrome: The Risk Factors(Revised edition with Citations)

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                                     Polycystic Ovarian Syndrome

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 cardiovasular disease(8)(13), acne(10)(14), endometrial cance(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 Risk factors


1. Family history
Risk of PCOs is increase if your mother or sister has PCOS(29). According to North Staffordshire Hospital, polycystic ovaries are highly prevalent within families as an autosomal dominant trait, in the analysis of 29 polycystic ovary syndrome and 10 control families(30).

2. Reproductive age women
Polycystic ovary syndrome (PCOS) affects 4% to 18% of reproductive-aged women(31)

3. Environment risks
a. Eating plastic-packaged food(32), fruit with pericarp(32) and drinking alcohol(32) were associated to the independent risk factors for PCOS. According to the Second Affiliated Hospital of Nanjing Medical University, risks of PCOs increased with the use of  disposable plastic cup for drinking, cooking oil fume and indoor decoration(33).
b. Exposure to industrial products such as Bisphenol A (BPA)(36)were found to exacerbate the clinical course of PCOS(34) as they exhibited impairment of normal reproductive function and metabolic regulation(35).

4. Dietary factor
Over-nutrition with foods in advanced glycated end products (AGEs) is found to associated to risk of PCOs(34).

5. Metabolic perturbations begin early in adolescence are also found to elevate risk of PCOs(37).

6. Psychotropic medication
Prolonged period uses of psychotropic drugs such as  mood stabilizers, lithium are also induced higher risk of PCOs(38). Women with epilepsy are also at risk of developed polycystic ovary syndrome (PCOS) if treated by valproate sodium (VPA) therapy(39)(40).

7. Genetic mutations
Although it is uncleared, genetic mutation of certain genes may be associated to the risk of PCOs, according to studies, such as the zona pellucida 4 (ZP4)(41) gene, polymorphism of FXIIIVal34Leu gene(42), C/T single nucleotide polymorphism at exon 17(43), single nucleotide polymorphism-56 of calpain-10 gene(44), vaspin rs2236242 polymorphism(45), etc.

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References
(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 With Polycystic 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)
(29) Hormonal abnormalities in first-degree relatives of women with polycystic ovary syndrome (PCOS) by Lenarcik A1, Bidzińska-Speichert B, Tworowska-Bardzińska U, Krępuła K.(PubMed)
(30) Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families by Govind A1, Obhrai MS, Clayton RN.(PubMed)
(31) Lifestyle changes in women with polycystic ovary syndrome. Moran LJ1, Hutchison SK, Norman RJ, Teede HJ.(PubMed)
(32) Environmental risk factors for women with polycystic ovary syndrome in china: a population-based case-control study by Zhang J1, Liu XF1, Liu Y1, Xu LZ1, Zhou LL1, Tang LL1, Zhuang J1, Li TT1, Guo WQ2, Hu R3, Qiu DS3, Han DW3.(PubMed)
(33) [Analysis of environmental factors and polycystic ovary syndrome]. [Article in Chinese] by Huang WJ1, Liu JY, Li LN.(PubMed)
(34) Phenotypes and enviromental factors: their influence in PCOS by Diamanti-Kandarakis E1, Christakou C, Marinakis E.(PubMed)
(35) Industrial endocrine disruptors and polycystic ovary syndrome by Palioura E1, Diamanti-Kandarakis E.(PubMed)
(36) Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS) by Rutkowska A1, Rachoń D.(PubMed)
(37) PCOS in adolescence and type 2 diabetes by Carreau AM1, Baillargeon JP.(PubMed)
(38) [Adverse events of psychotropic drugs]. [Article in Japanese] by Watanabe K, Kikuchi T.(PubMed)
(39) [Characteristics of women with epilepsy who developed polycystic ovary syndrome owing to the therapy with valproate sodium]. [Article in Japanese] Minagawa K1, Watanabe T, Oyanagi R.(PubMed)
(40) A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy by Hu X1, Wang J, Dong W, Fang Q, Hu L, Liu C.(PubMed)
(41) 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)
(42) Association study of polymorphism of FXIIIVal34Leu gene and polycystic ovary syndrome by  Wang X1, Yang Y1, Huang Y2, Wang Q3.(PubMed)
(43) [Correlation between single nucleotide polymorphism of insulin receptor gene with polycystic ovary syndrome]. [Article in Chinese] by Chen ZJ1, Shi YH, Zhao YR, Li Y, Tang R, Zhao LX, Chang ZH.(PubMed)
(44) [Relationship between single nucleotide polymorphism-56 of calpain-10 gene and glucose and lipid metabolism in polycystic ovary syndrome patients]. [Article in Chinese] by Diao XH1, Shi YH, Gao Q, Wang LC, Tang R, Chen ZJ.(PubMed)
(45) Association between vaspin rs2236242 gene polymorphism and polycystic ovary syndrome risk by Kohan L1, Zarei A2, Fallahi S3, Tabiee O4.(PubMed)