The Holistic prevention, management and treatment of Polycystic Ovarian Syndrome: The Complications (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).


                                   PCOs Complications

1. Cardiovascular diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease.  Women with PCOs have found to have increased risk of CVD due to hyperandrogenism in aggravation of abdominal obesity(211), insulin resistance forming(211), metabolic syndrome(212), type 2 diabetes(212)(213), altered plasma lipid profile(215), sympathovagal imbalance(216),.... According to University of Western Australia, treatment in  uncorrelated components, such as insulin resistance, dyslipidaemia/hypertension or hyperandrogenaemia may be effectively to reduce differing cardiometabolic outcomes(214). Non-medical (normalization of weight, healthy lifestyle) and medical (metformin, thiazolidinediones, spironolactone, and statins) interventions were found effectively in reduced long-term risk for cardiovascular morbidity and mortality in women with PCOs(217).
Conflictingly, according to the study by Division of General Internal Medicine, Mayo Clinic, although  women with PCOS weighed more than controls, there was no increased prevalence of other CV risk factors(218). The study also insisted that data on the incidence of CV events are lacking in PCOs' population(218)

2. Stroke
Besides cancer and heart diseases, stroke is the third leading cause of death. Approximate 1/4 of all stroke victims die as a direct result of the stroke or it's complications.  Epidemiological evidences suggested that women with PCOs are at increased risk of stroke(220)(221). According to the review of 1340 articles, 5 follow-up studies published between 2000 and 2008 conducted by Leiden University Medical Center,, risk of stroke of women with PCOs was 2 folds higher in comparison of women with PCOS to women without PCOS(219).
 
3. Endometrial cancer
Endometrium is the inner lining of the mammalian uterus and very susceptible hormone change, particular to menstrual cycle. Endometrial cancer is a late adulthood cancer defined as a condition of which the cells of the endometrial lining of uterus have growth uncontrollable or become cancerous as a result of the alternation of cells DNA. It's the fourth most common cancer among women overall, after breast cancer, lung cancer, and bowel cancer.
women with polycystic ovary syndrome (PCOS) with altered estrogen and/or abnormality of levels  progesterone (P₄) at gene level(222), mutation gene(223)(227), abnormal levels of hormone (gonadotropins, estrogens, androgens, prolactin, andserotonin and progesterone),(228), hyperandrogenism(224), abnormal menstrual pattern(225), insulin resistance(228) associated with PCOS and obesity(226)(228), may contribute to increased endometrial cancer risk(222). Metformin(229) and combination of  metformax, bromcriptine mesylate and metformin showed to improve clinical and metabolic syndrome in women with PCOS(230) with metformin alone through up-regulated tumor suppressor gene such as p53, cyclin D2 and BCL-2)(229).
 
4. Dyslipidemia 
Dyslipidemia, one of metabolic syndrome has found to be associated to many patients with polycystic ovary syndrome (PCOS) risk factor(233), chracterized by elevated low-density lipoprotein (LDL), triglyceride levels and decreased high-density lipoprotein (HDL)(234), probably different metabolic aetiologies depending on DHEA-S metabolism, independent to insulin concentrations(235).
According to University of Brescia, Italy, use of the oral contraceptive for suppressed gonadotropin and androgen values and increased the levels of sex hormone binding globulin in women with PCOs showed a significant increase in triglycerides, high density lipoprotein (HDL) cholesterol system(232). Phytochemicals Berberine and monacolin showed effectively in a balanced lipid profile, through improve lipid metabolism in oral contraceptive induced hypercholesterolemia in women with or without PCOS(231).

5. Pregnancy risk
Women with PCOs are associated to higher rate of early pregnancy loss in comparison to women with reproductive problems(237). According to joint study conducted by Norwegian University of Science and St Olavs Hospital, wone with PCOs are associated to pre term delivery in twin pregnancies(236). Treatment with N-acetylcysteine (NAC) showed to enhance higher odds of getting pregnant with a live birth(238). In subfertile women with anovulatory PCOS, letrozole improved live birth and pregnancy rates in comparison to clomiphene citrate(239).
Adding phytochemical Cimicifugae Racemosae to clomiphene-induction cycles with timed intercourse significantly improved cycle outcomes and pregnancy rates in women with polycystic ovarian(241). Traditional Chinese formula, Danzhi Xiaoyao Pill (DXP) effectively enhanced the ovulation rate and the clinical pregnancy rate of 60% in anovulation infertility patients with PCOS complicated IR(242).
Dr. Ried K. at National Institute of Integrative Medicine, Hawthorn, Melbourne, VIC, Australia said " Chinese herbal medicine can improve pregnancy rates 2-fold within a 3-6 month period compared with Western medical fertility drug therapy, including women with PCOS"(240).

6. Infertility(See diseases associated to PCOs)

7.  Higher risk of Gestational diabetes
Epidemiologocal studies, linking higher incidence of gestational diabetes mellitus (GDM) for women with PCOs has porduced inconsistent result(243)(244). Aristotle University suggested a improve  properly designed studies are necessary before any recommendation to pregnant women with PCOS in regard to the risk of GDM(245), But according to Imperial College School of Medicine, there is a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes(246).

8. Depression
Women with PCOS are found to have a higher rate of depression in comparison group women without(247)(248)(250). Psychologically, according to Institute of Psychology, Eötvös Loránd University, women with PCOs are associated with a great number of psychological symptoms, including (e.g. depression, anxiety, body image dissatisfaction, eating and sexual disorders, and low life satisfaction) due to gynaecological disorder of endocrine origin(249).

9. Liver diseases
Women with PCOS are associated to high risk of NAFLD(251)(252)(253). The suggested that some women with PCOS particularly those with an evidence of metabolic syndrome. should be considered to be screened for liver disease at an earlier age(254).

10. Diabetes(See diseases associated to PCOs)


Ovarian Cysts And PCOS Elimination
Holistic System In Existence That Will Show You How To
Permanently Eliminate All Types of Ovarian Cysts Within 2 Months   

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)
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(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)
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(22) Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro by Piltonen TT¹, Chen JC², Khatun M³, Kangasniemi M³, Liakka A⁴, Spitzer T², Tran N², Huddleston H², Irwin JC², Giudice LC⁵.(PubMed)
(223) The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome - a proof-of-concept study by Shafiee MN¹, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, Hatta AZ, Seedhouse C, Chapman C, Mokhtar NM.(PubMed)
(224) Micronized estradiol and progesterone therapy in primary, preinvasive endometrial cancer (1A/G1) in young women with polycystic ovarian syndrome by Stanosz S¹, von Mach-Szczypiński J, Sieja K, Koœciuszkiewicz J.(PubMed)
(225) The percentages of endometrial hyperplasia and endometrial cancer among polycystic ovary syndrome (PCOS) patients presenting with abnormal menstrual pattern by Prakansamut N, Sirayapiwat P, Triratanachat S.(PubMed)
(226) PCOS and obesity: insulin resistance might be a common etiology for the development of type I endometrial carcinoma by Li X1, Shao R2(PubMed)
(227) Mesenchymal stem/progenitors and other endometrial cell types from women with polycystic ovary syndrome (PCOS) display inflammatory and oncogenic potential by Piltonen TT1, Chen J, Erikson DW, Spitzer TL, Barragan F, Rabban JT, Huddleston H, Irwin JC, Giudice LC.(PubMed)
(229) The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome - a proof-of-concept study by Shafiee MN1, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, Hatta AZ, Seedhouse C, Chapman C, Mokhtar NM.(PubMed)
(230) Micronized estradiol and progesterone therapy in primary, preinvasive endometrial cancer (1A/G1) in young women with polycystic ovarian syndrome by Stanosz S1, von Mach-Szczypiński J, Sieja K, Koœciuszkiewicz J.(PubMed)
(231) Berberine and monacolin effects on the cardiovascular risk profile of women with oestroprogestin-induced hypercholesterolemia by Cicero AF1, Reggi A, Parini A, Morbini M, Rosticci M, Grandi E, Borghi C.(PubMed)
(232) Effects of long-term administration of an oral contraceptive containing ethinylestradiol and cyproterone acetate on lipid metabolism in women with polycystic ovary syndrome by Falsetti L1, Pasinetti E.(PubMed)
(233) Polycystic Ovary Syndrome and the Metabolic Syndrome by Julie L. Sharpless, MD(American diabeyes association)
(234) Pathophysiology and types of dyslipidemia in PCOS by Diamanti-Kandarakis E1, Papavassiliou AG, Kandarakis SA, Chrousos GP(PubMed)
(235) Dyslipidaemia in polycystic ovarian syndrome: different groups, different aetiologies? by Meirow D1, Raz I, Yossepowitch O, Brzezinski A, Rosler A, Schenker JG, Berry EM.(PubMed)
(236) Pregnancy and perinatal outcomes in women with polycystic ovary syndrome and twin births: a population-based cohort study by Løvvik TS1, Wikström AK, Neovius M, Stephansson O, Roos N, Vanky E.(PubMed)
(237) [Reproductive problems in women with PCOS, the impact of PAI-1 carriers of 4G PAI-1 polymorphism and BMI]. [Article in Russian] [No authors listed](PubMed)
(238) N-acetylcysteine for polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled clinical trials byThakker D1, Raval A2, Patel I3, Walia R4.(PubMed)
(239) Aromatase inhibitors for subfertile women with polycystic ovary syndrome by Franik S1, Kremer JA, Nelen WL, Farquhar C.(PubMed)
(240) Chinese herbal medicine for female infertility: an updated meta-analysis by Ried K1.(PubMed)
(241) Adding the phytoestrogen Cimicifugae Racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates - a randomized trial by Shahin AY1, Mohammed SA.(PubMed)
(242) [Effect of danzhi xiaoyao pill on ovulation induction of polycystic ovarian syndrome patients of pathogenic fire derived from stagnation of gan-qi]. [Article in Chinese] by Liu Y1, Mao LH.(PubMed)
(243) Prevalence of gestational diabetes mellitus in polycystic ovarian syndrome (PCOS) patients pregnant after ovulation induction with gonadotrophins by Vollenhoven B1, Clark S, Kovacs G, Burger H, Healy D.(PubMed)
(244) Prevalence of gestational diabetes mellitus and pregnancy outcomes in Asian women with polycystic ovary syndrome by Weerakiet S1, Srisombut C, Rojanasakul A, Panburana P, Thakkinstian A, Herabutya Y.(PubMed)
(245)
(246) The prevalence of polycystic ovaries in women with a history of gestational diabetes. Kousta E1, Cela E, Lawrence N, Penny A, Millauer B, White D, Wilson H, Robinson S, Johnston D, McCarthy M, Franks S.(PubMed)
(247) Reporting the rates of depression in polycystic ovary syndrome (PCOS) by Barry JA1, Kuczmierczyk AR, Hardiman PJ.(PubMed)
(248) Depression symptoms and body dissatisfaction association among polycystic ovary syndrome women by Pastore LM1, Patrie JT, Morris WL, Dalal P, Bray MJ.(PubMed)
(249) Psychological aspects of the polycystic ovary syndrome by Farkas J1, Rigó A, Demetrovics Z.(PubMed)
(250) Is having polycystic ovary syndrome a predictor of poor psychological function including anxiety and depression? by Deeks AA1, Gibson-Helm ME, Paul E, Teede HJ.(PubMed)
(251) Are women with polycystic ovarian syndrome at a high risk of non-alcoholic Fatty liver disease; a meta-analysis by Ramezani-Binabaj M1, Motalebi M2, Karimi-Sari H3, Rezaee-Zavareh MS1, Alavian SM4.(PubMed)
(252) Nonalcoholic fatty liver disease in women with polycystic ovary syndrome by  Cerda C1, Pérez-Ayuso RM, Riquelme A, Soza A, Villaseca P, Sir-Petermann T, Espinoza M, Pizarro M, Solis N, Miquel JF, Arrese M.(PubMed)
(253) [Prevalence of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome: a case-control study]. [Article in Chinese] by Zheng RH1, Ding CF.(PubMed)
(254) An association between non-alcoholic fatty liver disease and polycystic ovarian syndrome by  Brzozowska MM1, Ostapowicz G, Weltman MD(PubMed)