The Holistic Clinical Trials and Studies of Polycystic Ovarian Syndrome: The Stress Response and Management herbal Licorice

By Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
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Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.


                     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 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).

                     In Herbal Medicine Perspective

                 The prevention and management 

Polycystic ovary syndrome (PCOS) is unpreventable in Western medicine. Early diagnosis and treatment may reduce risk of its complications, including infertility, metabolic syndrome, obesity, diabetes, cardiovascular diseases, stroke, etc.
Reduce fat intake less than 30% of total calories with a low proportion of saturated fat and high in fiber from predominantly low-glycaemic-index-carbohydrate foods for patients with PCOs(827a). Calorie intake should be distributed between several meals per day with restricted intake of snacks and drinks(828).

The stress management herb: Licorice


Stress in a natural reaction of human fight or fight response induced by pressure due to such as an environmental condition or a stimulus. Long term stress can cause deleterious and cumulative effects on human body(1104), including emotional or cognitive problems, such as an increased risk of attentional deficit/hyperactivity, anxiety, and language delay(1103), especially for people with chronic illness, including women with Polycystic Ovarian Syndrome (PCOs)(1105).

(See herbal treatment of PCOs for more information)
[Gan Cao is also known as Licorice root. The sweet and neutral herb has been used in TCM as anti allergy(856), anti inflammation(855), anti ulcer(857), anti convulsion(858) agent and to treat stomach weakness, tired and lack of strength, cough with abundance of phlegm, stomach and solar plexus pain, and improve cardiac function(855), etc., as it tonifies the Spleen, benefits the Qi, moistens the Lungs, calms cough, deaf or acute pain, by enhancing all 12 channels(859).
In treatment of PCOs(862), combination of licorice and 100 mg spironolactone showed the activation of the renin-aldosterone system in lowering blood pressure and water (fluid) balance(860). reducing the prevalence of side effects related to the diuretic activity of spironolactone(860). In model rats experiment, Ganshao Paste (CGP), showed the decrease of serum levels of LH, T, and FSH and increase of serum estradiol (E2), and progesterone (P)(861)(865)].

(See The Insulin resistance improvement and/or anti metabolic syndrome herbs: Licorice for more information)
1. PCOs

[ Licorice, in a review of 33 studies of herbal medicine for the management ofpolycystic ovary syndrome (PCOS), showed a stronge evidences in improved metabolic hormone profile and improved fertility outcomes and regulation of ovulation and inhibition of hyperandrogenism in PCOS(860). In model rats experiment, Ganshao Paste (CGP), also decreased serum levels of LH, T, and FSH and increased of serum estradiol (E2), and progesterone (P)(861)(860)(865). According to University of Natural Resources and Life Sciences Vienna, licorice may have a potential effect on metabolic syndrome(862) in women with PCOs.

2. Blow flow
Licorice improves the blood flow in the body by exerting its anti thrombosis(983) and inhibiting the levels of bad cholesterol(984)(985) and triglyceride levels(985) and increasing HDL-cholesterol content(984) in reduced risk of cardiovascular disease(985) and blood stagnation(897) in the abdominal region induced induced infertility(986).

3. Glycyrrhizin
Glycyrrhizin, one of main ingredient from licorice, exhibited anti inflammatory effect pharmacologically in treatment of inflammatory diseases(988)(989)(990), lowered high serum testosterone levels in oligomenorrheic or amenorrheic women, and induced conception in some women(991). As antioxidant, the phytochemical also inhibit irregular cell growth(992)(993) and microbial invasion(994)(995) causes of cancers(992)(993) and infection and inflammation(994)(995) respectively. in adrenocortical function and behavour, it also regulated the levels of cortisol(996), induced by over production of serotonin cause of hormone imbalance(997).

4. Phytoestrogen
See phytoestrogen in black cohosh
[Phytoestrogen found it balck cohosh showed to occupy the estrogen receptor sites in women body(908), through it antiestrogenic and extrogenic effects(909), to induce hormone balancing may result in improving the chance of ovulation and fertility(910)(911)].

5. Lecithin
Lecithin is a fat like substance called a phospholipid improved lipid transfer, cholesterol efflux, HDL genesis and and remodeling at the blood-brain barrier (BBB)(998). against cells from oxidation surrounding the brain(999), in reducing psychotic symptoms(1002) such as stress(1000)(1001), and depression(1002).
Side effects
1. It may raise blood pressure(1003)(1004(1006)
2. Long term usage of large dosage can also cause edema(1004)(1006) and hypokalemia(1004)(1005)(1006).
3. Overdose can be toxic(106), in inducing rhabdomyolysis or myoglobinuria(1006).
4. Etc.]
Phytochemicals(1058)
1. Glycyrrhizic acid
2. Licochalcone A
3. Licochalcone B
4. Licoflavone
5. Liquiritin
5. Liquiritigenin
7. Isoliquiritigenin
8. Ononins
9. 4′，7-dihydroxyflavone
10. Glycyrrhetinic acid
11. 11-deoxyglycyrrhetinic acid
12. β-sitosterol
13. Etc.

Licorice's phytochemicals, especially glycyrrhizin, have shown efffectively in ameliorated insulin resistance(1059)(1061)(1063)(1064), hyperglycemia(1059)(1060), dyslipidemia(1059)(1063) and oxidative stress(1064) in fructose-induced metabolic syndrome(1059)(1061)(1063) in animal(1059)(1060)(1061)models, probably through its interference of the development of visceral obesity(1064) and cellular derailments that are responsible for the development of metabolic syndrome(1062), anti inflammatory(1062), antioxidant(1062) and an associated with a decrease in tissue lipid deposition(1063) effects].

In chronic unpredictable stress rat model, total flavonoids extract(1153) (licorice flavonoids, LF) and liquiritin(1154), a phyochemical found in locorice exerted anti-depressive(1153)(1154)(1155) and anti-cognitive impairment(1156) property through total flavonoids extract neurogenesis protective effect(1153) and defense of liquiritin and flavonoids extract against oxidative stress(1154)(1156).
Yokukansan, a traditional Japanese formula, containing licorice showed effectively in amelioration of behavioral symptoms, such as aggressiveness, excitability, and hallucination, through reduced stress increased the serotonin 2A (5-HT2A) receptors density on the plasma membrane of the prefrontal cortex (PFC)(1158).
In high-glucose stress, Glabridin(1159)(1160), an isoflavan from licorice root reduced high-glucose stress(1159)(1160) through its anti inflammatory activity(1159), up-regulates manganese superoxide dismutase, catalase and paraoxonase 2(1160).
In anti oxidative stress, licorice showed to contribute to their overall health promoting pharmacological effects against free radicals(1161)(1162)(1163)(1164) induced diseases such as cancer(1161), cardiac dysfunction(1162) liver diosease(1164), etc., through its anti-inflammatory(1161)(1163)(1164), anti-oxidant activities(1161)(1162)(1163)(1164).
According to University of Western Sydney, Glycyrrhiza glabra, one of Chinese herbs, exhibited strong evidences of neuroprotective activity for promotion of healthy ageing and longevity(1157).

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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 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)
(827a) Diet and nutrition in polycystic ovary syndrome (PCOS): pointers for nutritional management by Farshchi H, Rane A, Love A, Kennedy RL(PubMed)
(828) The optimal diet for women with polycystic ovary syndrome? by Marsh K, Brand-Miller J.(PubMed) (1106) Simultaneous Estimation of Withaferin A and Z-Guggulsterone in Marketed Formulation by RP-HPLC by Agrawal P1, Vegda R2, Laddha K2.(PubMed)
(1153) [Antidepressant activities of flavonoids from Glycyrrhiza uralensis and its neurogenesis protective effect in rats].[Article in Chinese] by Fan ZZ1, Zhao WH, Guo J, Cheng RF, Zhao JY, Yang WD, Wang YH, Li W, Peng XD.(PubMed)

(1154) Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis inchronic variable stress induced depression model rats by Zhao Z1, Wang W, Guo H, Zhou D.(PubMed)
(1155) Metabonomic study on chronic unpredictable mild stress and intervention effects of Xiaoyaosan in rats using gas chromatography coupled with mass spectrometry by Gao X1, Zheng X, Li Z, Zhou Y, Sun H, Zhang L, Guo X, Du G, Qin X.(PubMed)
(1156) Neuroprotective effects of flavonoids extracted from licorice on kainate-induced seizure in mice through their antioxidant properties by Zeng LH1, Zhang HD, Xu CJ, Bian YJ, Xu XJ, Xie QM, Zhang RH.(PubMed)

(1157) An in vitro study of neuroprotective properties of traditional Chinese herbal medicines thought to promote healthy ageing and longevity by Shen B, Truong J, Helliwell R, Govindaraghavan S, Sucher NJ1.(PubMed)
(1158) Yokukansan, a traditional Japanese medicine, decreases head-twitch behaviors and serotonin 2A receptors in the prefrontal cortex of isolation-stressed mice, by Ueki T1, Mizoguchi K2, Yamaguchi T2, Nishi A2, Sekiguchi K2, Ikarashi Y2, Kase Y2.(PubMed)
(1159) Glabridin, an isoflavan from licorice root, downregulates iNOS expression and activity under high-glucose stress and inflammation by Yehuda I1, Madar Z, Leikin-Frenkel A, Tamir S.(PubMed)
(1160) Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose stress by Yehuda I1, Madar Z, Szuchman-Sapir A, Tamir S.(PubMed)
(1161) Anti-inflammatory/Anti-oxidative stress activities and differential regulation of Nrf2-mediated genes by non-polar fractions of tea Chrysanthemum zawadskii and licorice Glycyrrhiza uralensis by Wu TY1, Khor TO, Saw CL, Loh SC, Chen AI, Lim SS, Park JH, Cai L, Kong AN.(PubMed)
(1162) Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury by Ojha SK1, Sharma C1, Golechha MJ1, Bhatia J1, Kumari S2, Arya DS3.(PubMed)
(1163) Licochalcone A activates Nrf2 in vitro and contributes to licoriceextract-induced lowered cutaneous oxidative stress in vivo by Kühnl J1, Roggenkamp D, Gehrke SA, Stäb F, Wenck H, Kolbe L, Neufang G.(PubMed)
(1164) 18-β Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: Role in hyperproliferation, inflammation andoxidative stress by Hasan S1, Khan R1, Ali N1, Khan A1, Rehman M1, Tahir M1, Lateef A1, Nafees S1, Mehdi S1, Rashid S1, Shahid A1, Sultana S2.(PubMed)