Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 20  |  Issue : 2  |  Page : 89-94

Polycystic ovary syndrome: Current perspectives and recent advances


1 Department of Public Health Research, Indian Institute of Public Health, Hyderabad, Telangana, India
2 Department of Obstetrics and Gynecology, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chennai, Tamil Nadu, India
3 Department of Community Medicine, Chettinad Academy of Research and Education, Chennai, Tamil Nadu, India

Date of Submission06-Jan-2022
Date of Decision17-Feb-2022
Date of Acceptance31-Mar-2022
Date of Web Publication07-May-2022

Correspondence Address:
Dr. D Vinoth Gnana Chellaiyan
Department of Community Medicine, Chettinad Academy of Research and Education, Kelambakkam, Chennai - 603 103, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/cmi.cmi_2_22

Rights and Permissions
  Abstract 


Excess ovarian activity, chronic anovulation, and androgen excess are the common traits of polycystic ovary syndrome (PCOS). Several advances have been made in understanding the pathophysiology in the process of finding quicker and more effective management measures. Androgen excess in PCOS was found to correlate with markedly elevated luteinizing hormone pulsatility. Impaired insulin response is also attributed to PCOS. Regimen with 3 mg drospirenone + 20 μg ethinyl estradiol combination is beneficial for hormonal imbalance and lipid profile while having a substantial safety profile. Clinical evidence has demonstrated that a 40:1 combination of Myo-inositol and D-chiro-inositol restores ovulation in PCOS women. For women with clomiphene citrate-resistant PCOS, laparoscopic ovarian drilling has proved to be a safe and effective surgical alternative. PCOS is also an indication of bariatric surgery. To conclude, constitutional management by a multidisciplinary team may be helpful for women with PCOS. Lifestyle interventions are best advised and, in so doing, decrease body adiposity and recuperate their metabolic and reproductive health.

Keywords: Bariatric surgery, polycystic ovary syndrome, recent advances, Stein–Leventhal


How to cite this article:
Nirupama A Y, John JB, Chellaiyan D V. Polycystic ovary syndrome: Current perspectives and recent advances. Curr Med Issues 2022;20:89-94

How to cite this URL:
Nirupama A Y, John JB, Chellaiyan D V. Polycystic ovary syndrome: Current perspectives and recent advances. Curr Med Issues [serial online] 2022 [cited 2022 May 21];20:89-94. Available from: https://www.cmijournal.org/text.asp?2022/20/2/89/344932




  Introduction Top


Stein–Leventhal syndrome, popularly known as polycystic ovary syndrome (PCOS), is one of the foremost causes of female infertility.[1] The “Rotterdam Consensus” in 2003, held conjointly by the North American and European Associations of Reproductive Medicine, stated that the occurrence of any two out of the following features will be considered as diagnostic criteria for PCOS: hyperandrogenism (clinical or laboratory), ovulatory dysfunction (characterized by irregularities in menstrual cycles), or polycystic ovarian morphology by ultrasound.[2] The prevalence of PCOS among women of reproductive age group ranges from 4% to 20% globally and 3.7% to 22.5% nationally in India, depending on the population studied and the criteria used for diagnosis.[3],[4]

As expressed, PCOS is a multidimensional disorder depicted by an amalgamation of signs and symptoms of ovarian dysfunction and androgen excess without another identifiable diagnosis.[5] Unlike erstwhile causes of anovulation involving ovarian inactivity or primary insufficiency, PCOS presents with chronic anovulation in the presence of hyperactivity of the ovaries.[6] In addition to synchronicity of insulin resistance (IR) and obesity, the effect of androgen excess is considered the driving force behind the inflammatory and metabolic instabilities associated with PCOS.[6] High circulating testosterone levels have been demonstrated in PCOS, produced either from the ovary (where androgen production is controlled by luteinizing hormone [LH] levels) or adrenal or both.[7]

The past decade has witnessed several advances in understanding the underlying pathophysiological mechanisms of PCOS, leading to further advancement in the scope for independent diagnosis and effective multidisciplinary management of PCOS.


  Pathophysiology Top


In a contemporary genome-wide meta-analysis incorporating over 10,000 cases of PCOS, 14 independent loci (including three novel loci) linked with increased risk for PCOS were identified. No difference whatsoever was observed in the association between various clinical phenotypes and a major portion of the PCOS-susceptibility loci, implying similar underlying genetic traits for the various phenotypes.[8]

The ongoing search for the likely driving forces behind increased androgen secretion in PCOS led to the findings of markedly elevated LH pulsatility in letrozole-treated mice, compared to that in PCOS women. This hyperactive LH pulse secretion may be attributed to the increased hypothalamic kisspeptin and neurokinin B levels.[9] Disconcerted gonadotropin-releasing hormone (GnRH) pulsatility is reported as an alternative reason for increased LH pulsatility.[10] Intracerebroventricular administration of anti-Müllerian hormone (AMH) was reported to increase GnRH-dependent LH pulsatility due to the expression of AMH receptors in GnRH neurons.[11]

The constructive effects of exercise on metabolism can be attributed to “irisin,” a myokine induced by exercise. A recent systematic review meta-analysis (SRMA) stated that PCOS patients seem to have standard irisin levels after adjustment for body mass index (BMI). Nevertheless, the response of “irisin” to hyperinsulinemia may be weakened in women with PCOS.[12]


  Risk Factors for Polycystic Ovary Syndrome Top


Positive family history, obesity/weight gain, history of epilepsy, diabetes, etc., have been identified as risk factors for PCOS among women in the reproductive age group.[13],[14],[15],[16],[17] Girls born to obese/overweight women, low birth weight, and congenital virilization were identified to increase the risk of PCOS in children. Irregular menstruation, premature pubarche, obesity syndromes, and acanthosis nigricans are a few of the risk factors evident later in childhood.[18],[19]

IR has been demonstrated widely in women with PCOS. This has been shown to occur independent of obesity, and the effect of obesity was additive to the effect of PCOS on IR.[20] A recent SRMA studied literature with BMI-matched controls and showed a higher prevalence of metabolic syndrome in women with PCOS compared to women without PCOS (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.36–3.56).[21]


  Polycystic Ovary Syndrome and COVID-19 Pandemic Top


Ethnic predisposition, hyperinflammation, hyperandrogenism, and low Vitamin D levels are certain factors that have been strongly associated with PCOS as well as a risk of severe COVID-19.[22] Along with these, women in the reproductive age group are highly prone to multiple cardiometabolic conditions, such as type 2 diabetes, hypertension, obesity, and alterations in the gut microbiome, which increase the risk for adverse COVID-19–related outcomes. This strong overlap of risk factors for PCOS and severe COVID-19 should be highlighted since women with PCOS tend to receive care from multiple health services.[20],[22],[23]

In obese/overweight women, a minimum of 5% weight loss has been associated with increased fertility and improved pregnancy outcomes. This was a major challenge during the lockdown due to COVID-19 pandemic, which led to a drastic lowering of success in weight loss programs despite adaptations.[24] This not only added to the already existing challenges of living with PCOS but also had a detrimental effect on their mental health. A high level of anxiety and stress was experienced by them due to uncertainty about their increased risk for COVID-19 and lack of support strategies due to limitations imposed on healthcare services.[25]


  Diagnosis Top


Updated diagnostic guidelines from the International PCOS Network endorsed the use of “Rotterdam criteria” in adults and the combined presence of hyperandrogenism and oligo-anovulation in adolescents.[26] Hyperandrogenism is reported in about 60%–80% of PCOS cases established by the Rotterdam criteria.[6] As long as “biochemical hyperandrogenism” persists as a diagnostic challenge deprived of an affordable, sensitive, reproducible, and validated testosterone assay, its assessment to diagnose PCOS should be subject to sex hormone-binding globulin, total serum testosterone, and free androgen index.[27]

Existing evidence points toward a key role for adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) in the intra-ovary adiponectin, insulin, and follicle-stimulating hormone (FSH) signaling pathways. Recent studies on mouse model systems point toward the potential role of APPL in preventing IR, diabetes, and endothelial disorders. With APPL1 deficiency leading to metabolic and vascular disorders, APPL1 is now an innovative diagnostic and therapeutic option for ovarian dysfunctions and reproductive disorders, particularly PCOS.[28]


  Management: Lifestyle and Behavioral Approaches Top


“International evidence-based guideline (2018) for the assessment and management of PCOS” recommends lifestyle interventions such as diet, exercise, and behavioral approaches for all women with PCOS. An earlier study on a hyperandrogenic PCOS mouse model revealed that PCOS traits were augmented selectively by diet. Reproductive traits were shown to have a greater sensitivity to dietary macronutrient balance than metabolic traits, suggesting that the development of evidence-based dietary interventions would be a hopeful strategy for PCOS management, specifically for reproductive traits.[29]

Lifestyle and behavioral approach (LBA) has always been considered the first line of treatment for PCOS, especially in overweight/obese women.[30] Despite substantial evidence-based guidelines, the intensity, complexity, and behavioral components of lifestyle modifications are not clearly understood, and 45% of women with PCOS report that LBA was never suggested as a management alternative.[31],[32] Increased physical activity, dietary alterations, and weight loss have been suggested as some of the first-line lifestyle interventions for women with PCOS.[30],[33],[34] LBA should also include changes in alcohol use, psychosocial stress, and tobacco consumption, for long-term management of PCOS.[34] LBA has found maximum effect in PCOS women with obesity or hyperglycemia but no significant effect on ovulation complications and hyperandrogenicity in nonobese women.[33] In the current situation of the COVID-19 pandemic, lockdowns, quarantine, and isolation, maintaining good physical activity and monitoring diet are proving to be the major challenges for women with PCOS.

PCOS and weight gain have always gone hand-in-hand. Weight loss, maintenance of weight loss, and prevention of weight gain are hence significant in women with PCOS.[32] Evidence suggests that short-term weight loss is successful in decreasing IR and restoring fertility.[34] However, most often, then, women are faced with the challenge of sustainable weight loss. Inclusion of social support, motivation, and psychological and behavioral strategies such as goal setting and self-monitoring can give better weight loss outcomes.[32]

A recent SRMA of 14 trials involving 517 women reported that a significant decrease in waist circumference, fasting glucose, lipid levels, and systolic blood pressure was noted with exercise. However, they went on mention that the effect of exercise on reproductive function was unclear. Quantitatively, there were insufficient published data, but semi-quantitative analysis suggested improvement in menstrual regularity and pregnancy outcomes.[35]

A total of 583 women in nine trials comparing those who received LBA with those who either received metformin or minimal intervention or no intervention were taken up in an SRMA. A lifestyle modification significantly reduces fasting glucose (weighted mean difference, −2.3 mg/dL; P = 0.04) and fasting insulin (weighted mean difference, −2.1 μU/mL; P < 0.001) when compared to minimal intervention. Surprisingly, the betterment in blood glucose or insulin levels noted with metformin was not significantly different from that due to LBA.[33]


  Management: Pharmaceutical Top


Oral contraceptives combined with antiandrogens continue to be the standard management regimen to bring down androgen levels and treat symptoms while simultaneously offering endometrial protection.[36] They act by suppressing ovulation through negative feedback on the hypothalamus and, at the same time, decreasing ovarian androgen secretion.[37] Recent evidence also suggests that treatment of PCOS patients with 3 mg drospirenone + 20 μg ethinyl estradiol combination is beneficial for hormonal imbalance and lipid profile while having a substantial safety profile.[38]

Clomiphene citrate (CC) continues to be the management choice for ovulation induction in anovulatory PCOS women. An alternative of 2.5 mg/day letrozole (aromatase inhibitor) has been suggested to induce ovulation in CC therapy failure patients. Evidence from an open-label randomized clinical trial in 2017 proposes that letrozole is better than metformin–CC combination to induce ovulation and clinical pregnancy. A higher rate of ovulation of 82% was reported among the patients in the letrozole arm, as opposed to the 43.1% in metformin–CC arm (P < 0.001). The participants in the letrozole arm also reported higher clinical pregnancy rate (36% vs. 9.8%, P < 0.001), higher multiple pregnancy rate (P < 0.05), better endometrial thickness (P < 0.001), more dominant follicles (P < 0.05), lesser adverse effects (P < 0.05), and higher acceptability (P < 0.001) compared to patients in the CC and metformin arm.[39] Clomiphene acts by blocking the hypothalamic–pituitary axis from circulating estrogen. Being structurally similar to estrogen, clomiphene blocks hypothalamic receptors and thus triggers FSH release from the anterior pituitary following alterations in GnRH pulsatility.[40]

Insulin-sensitizing agents, Myo-inositol and D-chiro-inositol, act as second messengers in insulin signaling, which are likely substitutes to metformin in PCOS with IR (IR-PCOS) by significantly reducing the theca/granulosa cell layer thickness ratio and the time to pregnancy.[41] Given the existing body of evidence, it can be said that inositol therapy can be an alternative for metabolic improvement in metformin-intolerant PCOS women. Clinical evidence has exhibited that an optimal 40:1 combination of Myo-inositol and D-chiro-inositol restores ovulation in PCOS women. Often, inositol-based PCOS regimens are randomly chosen doses and combined with useless or counter-productive molecules, thereby weakening the efficacy of Myo-inositol.[42] A trial on teenagers with PCOS reported that after receiving Myo-inositol, significant reduction in weight, BMI, glucose, C-peptide, insulin, and LH was detected. At the same time, the Oral Contraceptive pill (OCP) arm reported slight increase in weight and BMI slightly increased, while the metabolic parameters remained unchanged.[43]

An experimental study on female SpragueDawley rats showed that MitoQ10 (mitochondria-targeted antioxidant) may have a positive therapeutic effect on animals with IR-PCOS. The fortification of mitochondrial functions and the adaptation of programmed cell death-related proteins have been suggested as the most likely reasons behind this effect.[44]


  Management: Surgical Top


Since 1984, laparoscopic ovarian drilling (LOD) has advanced into a highly effective and safe surgical treatment for PCOS women, impassive to CC therapy. It mirrors the effects of gonadotropins using pregnancy and live births excluding risks of ovarian hyperstimulation or multiple pregnancies, along with a marked improvement in ovarian responsiveness to succeeding therapy with ovulation induction agents.[45]

Irrespective of the presence or absence of other causes of infertility, women with PCOS often have a receptivity defect in the endometrium which subsequently affects their fertility status. LOD also produces a substantial increase in the endometrial mRNA expressions (HOXA-10 and HOXA-11) and improvement in endometrial receptivity in CC-resistant PCOS.[46] In terms of ovarian drilling, bilateral LOD technique was shown to be more effective than the unilateral in terms of menstrual cycle regularity, ovulation induction, and snowballing pregnancy rates in women with CC-resistant PCOS.[47]

Endometrial hyperplasia and PCOS (both of which are related to an amplified risk for developing endometrial carcinoma) have been identified as hypothetically novel indications for bariatric surgery. Bariatric surgeries have been shown to improve most of the crucial diagnostic features seen in PCOS and women with ovarian volume.[48],[49] Some of the foremost bariatric procedures in the present era are laparoscopic adjustable gastric banding, laparoscopic sleeve gastrectomy, and Roux-en-Y gastric bypass.[48] The likelihood of a metabolic benefit from the surgical procedure could be achieved by the assessment of free testosterone levels.[49],[50]


  Management: Other Practices of Medicine Top


PCOS has always been a well-explored field with many complementary medical practices coming up with possible remedies from their diverse knowledge spectrum. Irrespective of whether it is the administration of the Chinese traditional herbal medicine, Cangfu Daotan decoction, role of gut microbiota, or the use of Yoga and Ayurvedic herbal mixtures, or the effect of homeopathic formulations such as Calcarea carbonica in improving menstrual regularity, there are a vast variety of probable remedies being suggested for PCOS.[51],[52],[53],[54],[55],[56]


  Complications Top


A 2017 meta-analysis presented a greater prevalence of nonalcoholic fatty liver disease (NAFLD) among women with hyperandrogenic PCOS compared to other PCOS phenotypes (OR [95% CI] = 2.54 [2.19–2.95]). The odds remained significantly high even after adjusting for confounding variables. Subsequently, elevated serum androgen levels were noted in PCOS women presenting with NAFLD compared to those without (mean difference [95% CI] = 0.40 [0.29–0.50] nmol/L).[57]

Irrespective of age, the risk and severity of stroke can be regulated by gonadal hormones. A growing body of evidence shows that continued gonadal hormone dysfunction in PCOS results in hyperandrogenism and metabolic comorbidities, which in turn is accompanied by an increased risk of stroke.[58]


  Conclusions Top


Updated acumens into the interrelation between brain, fat, muscle, and ovarian tissue aid the concept of PCOS being a systemic syndrome. The metabolic and inflammatory instabilities associated with PCOS can be partly explained by the co-existence of obesity and IR but are reinforced by hyperandrogenicity. The management plan should hence be custom-made, taking into consideration the patient phenotype, complaints, and planning for the family. Medical treatments have seen only insignificant advances in recent years. The increased effectiveness of aromatase inhibitor letrozole over CC to treat infertility due to PCOS may be considered noteworthy. Evidence for the positive effect of bariatric surgery in relieving PCOS symptoms can be taken as a positive step toward the future of interdisciplinary approaches in PCOS management. To conclude, constitutional management by a multidisciplinary team may be helpful for women with PCOS. Lifestyle interventions are best advised and, in so doing, decrease body adiposity and recuperate their metabolic and reproductive health.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Li Y, Chen C, Ma Y, Xiao J, Luo G, Li Y, et al. Multi-system reproductive metabolic disorder: Significance for the pathogenesis and therapy of polycystic ovary syndrome (PCOS). Life Sci 2019;228:167-75.  Back to cited text no. 1
    
2.
Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004;81:19-25.  Back to cited text no. 2
    
3.
Deswal R, Narwal V, Dang A, Pundir CS. The prevalence of polycystic ovary syndrome: A brief systematic review. J Hum Reprod Sci 2020;13:261-71.  Back to cited text no. 3
  [Full text]  
4.
Ganie MA, Vasudevan V, Wani IA, Baba MS, Arif T, Rashid A. Epidemiology, pathogenesis, genetics & management of polycystic ovary syndrome in India. Indian J Med Res 2019;150:333-44.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Escobar-Morreale HF. Polycystic ovary syndrome: Definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018;14:270-84.  Back to cited text no. 5
    
6.
Rocha AL, Oliveira FR, Azevedo RC, Silva VA, Peres TM, Candido AL, et al. Recent advances in the understanding and management of polycystic ovary syndrome. F1000Res 2019;8:v1000-565.  Back to cited text no. 6
    
7.
Kero J, Poutanen M, Zhang FP, Rahman N, McNicol AM, Nilson JH, et al. Elevated luteinizing hormone induces expression of its receptor and promotes steroidogenesis in the adrenal cortex. J Clin Invest 2000;105:633-41.  Back to cited text no. 7
    
8.
Day F, Karaderi T, Jones MR, Meun C, He C, Drong A, et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genet 2018;14:e1007813.  Back to cited text no. 8
    
9.
Esparza LA, Schafer D, Ho BS, Thackray VG, Kauffman AS. Hyperactive LH pulses and elevated kisspeptin and NKB gene expression in the arcuate nucleus of a PCOS mouse model. Endocrinology 2020;161:bqaa018.  Back to cited text no. 9
    
10.
Katulski K, Podfigurna A, Czyzyk A, Meczekalski B, Genazzani AD. Kisspeptin and LH pulsatile temporal coupling in PCOS patients. Endocrine 2018;61:149-57.  Back to cited text no. 10
    
11.
Cimino I, Casoni F, Liu X, Messina A, Parkash J, Jamin SP, et al. Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion. Nat Commun 2016;7:10055.  Back to cited text no. 11
    
12.
Cai X, Qiu S, Li L, Zügel M, Steinacker JM, Schumann U. Circulating irisin in patients with polycystic ovary syndrome: A meta-analysis. Reprod Biomed Online 2018;36:172-80.  Back to cited text no. 12
    
13.
Legro RS, Driscoll D, Strauss JF 3rd, Fox J, Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A 1998;95:14956-60.  Back to cited text no. 13
    
14.
Allahbadia G, Agrawal R. Polycystic Ovary Syndrome. Kent: Anshan Ltd; 2007. p. 536.  Back to cited text no. 14
    
15.
Herzog AG. Menstrual disorders in women with epilepsy. Neurology 2006;66 Suppl 3:S23-8.  Back to cited text no. 15
    
16.
Escobar-Morreale HF, Roldán B, Barrio R, Alonso M, Sancho J, de la Calle H, et al. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab 2000;85:4182-7.  Back to cited text no. 16
    
17.
Conn JJ, Jacobs HS, Conway GS. The prevalence of polycystic ovaries in women with type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2000;52:81-6.  Back to cited text no. 17
    
18.
Rosenfield RL. Clinical review: Identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2007;92:787-96.  Back to cited text no. 18
    
19.
Nicandri KF, Hoeger K. Diagnosis and treatment of polycystic ovarian syndrome in adolescents. Curr Opin Endocrinol Diabetes Obes 2012;19:497-504.  Back to cited text no. 19
    
20.
Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013;6:1-13.  Back to cited text no. 20
    
21.
Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod Update 2010;16:347-63.  Back to cited text no. 21
    
22.
Kyrou I, Karteris E, Robbins T, Chatha K, Drenos F, Randeva HS. Polycystic ovary syndrome (PCOS) and COVID-19: An overlooked female patient population at potentially higher risk during the COVID-19 pandemic. BMC Med 2020;18:220.  Back to cited text no. 22
    
23.
Subramanian A, Anand A, Adderley NJ, Okoth K, Toulis KA, Gokhale K, et al. Increased COVID-19 infections in women with polycystic ovary syndrome: A population-based study. Eur J Endocrinol 2021;184:637-45.  Back to cited text no. 23
    
24.
Šuštaršič A, Vrtačnik Bokal E, Burnik Papler T. The impact of COVID-19 lockdown on weight loss program in infertile polycystic ovary syndrome women with obesity. Obes Facts 2021;14:650-7.  Back to cited text no. 24
    
25.
Atkinson L, Kite C, McGregor G, James T, Clark CC, Randeva HS, et al. Uncertainty, anxiety and isolation: Experiencing the COVID-19 pandemic and lockdown as a woman with polycystic ovary syndrome (PCOS). J Pers Med 2021;11:952.  Back to cited text no. 25
    
26.
Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, et al. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril 2018;110:364-79.  Back to cited text no. 26
    
27.
Keck C, Tempfer CB, Hugues JN. Conservative Infertility Management. Florida: CRC Press; 2016. p. 210.  Back to cited text no. 27
    
28.
Artimani T, Najafi R. APPL1 as an important regulator of insulin and adiponectin-signaling pathways in the PCOS: A narrative review. Cell Biol Int 2020;44:1577-87.  Back to cited text no. 28
    
29.
Rodriguez Paris V, Solon-Biet SM, Senior AM, Edwards MC, Desai R, Tedla N, et al. Defining the impact of dietary macronutrient balance on PCOS traits. Nat Commun 2020;11:5262.  Back to cited text no. 29
    
30.
Bates GW, Legro RS. Longterm management of Polycystic Ovarian Syndrome (PCOS). Mol Cell Endocrinol 2013;373:91-7.  Back to cited text no. 30
    
31.
Aly JM, Decherney AH. Lifestyle modifications in PCOS. Clin Obstet Gynecol 2021;64:83-9.  Back to cited text no. 31
    
32.
Brennan L, Teede H, Skouteris H, Linardon J, Hill B, Moran L. Lifestyle and behavioral management of polycystic ovary syndrome. J Womens Health (Larchmt) 2017;26:836-48.  Back to cited text no. 32
    
33.
Domecq JP, Prutsky G, Mullan RJ, Hazem A, Sundaresh V, Elamin MB, et al. Lifestyle modification programs in polycystic ovary syndrome: Systematic review and meta-analysis. J Clin Endocrinol Metab 2013;98:4655-63.  Back to cited text no. 33
    
34.
Norman RJ, Davies MJ, Lord J, Moran LJ. The role of lifestyle modification in polycystic ovary syndrome. Trends Endocrinol Metab 2002;13:251-7.  Back to cited text no. 34
    
35.
Benham JL, Yamamoto JM, Friedenreich CM, Rabi DM, Sigal RJ. Role of exercise training in polycystic ovary syndrome: A systematic review and meta-analysis. Clin Obes 2018;8:275-84.  Back to cited text no. 35
    
36.
Luque-Ramírez M, Nattero-Chávez L, Ortiz Flores AE, Escobar-Morreale HF. Combined oral contraceptives and/or antiandrogens versus insulin sensitizers for polycystic ovary syndrome: A systematic review and meta-analysis. Hum Reprod Update 2018;24:225-41.  Back to cited text no. 36
    
37.
Shah D, Patil M; National PCOS Working Group. Consensus statement on the use of oral contraceptive pills in polycystic ovarian syndrome women in India. J Hum Reprod Sci 2018;11:96-118.  Back to cited text no. 37
[PUBMED]  [Full text]  
38.
Li L, Zhang R, Zeng J, Ke H, Peng X, Huang L, et al. Effectiveness and safety assessment of drospirenone/ethinyl estradiol tablet in treatment of PCOS patients: A single center, prospective, observational study. BMC Womens Health 2020;20:39.  Back to cited text no. 38
    
39.
Rezk M, Shaheen AE, Saif El-Nasr I. Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: A randomized clinical trial. Gynecol Endocrinol 2018;34:298-300.  Back to cited text no. 39
    
40.
Kamath MS, George K. Letrozole or clomiphene citrate as first line for anovulatory infertility: A debate. Reprod Biol Endocrinol 2011;9:86.  Back to cited text no. 40
    
41.
Bevilacqua A, Dragotto J, Giuliani A, Bizzarri M. Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J Cell Physiol 2019;234:9387-98.  Back to cited text no. 41
    
42.
Roseff S, Montenegro M. Inositol treatment for PCOS should be science-based and not arbitrary. Int J Endocrinol 2020;2020:6461254.  Back to cited text no. 42
    
43.
Pkhaladze L, Barbakadze L, Kvashilava N. Myo-inositol in the treatment of teenagers affected by PCOS. Int J Endocrinol 2016;2016:1473612.  Back to cited text no. 43
    
44.
Ding Y, Jiang Z, Xia B, Zhang L, Zhang C, Leng J. Mitochondria-targeted antioxidant therapy for an animal model of PCOS-IR. Int J Mol Med 2019;43:316-24.  Back to cited text no. 44
    
45.
Mitra S, Nayak PK, Agrawal S. Laparoscopic ovarian drilling: An alternative but not the ultimate in the management of polycystic ovary syndrome. J Nat Sci Biol Med 2015;6:40-8.  Back to cited text no. 45
    
46.
Senturk S, Celik O, Dalkilic S, Hatirnaz S, Celik N, Unlu C, et al. Laparoscopic ovarian drilling improves endometrial homeobox gene expression in PCOS. Reprod Sci 2020;27:675-80.  Back to cited text no. 46
    
47.
El-Sayed ML, Ahmed MA, Mansour MA, Mansour SA. Unilateral versus bilateral laparoscopic ovarian drilling using thermal dose adjusted according to ovarian volume in CC-resistant PCOS, A randomized study. J Obstet Gynaecol India 2017;67:356-62.  Back to cited text no. 47
    
48.
Charalampakis V, Tahrani AA, Helmy A, Gupta JK, Singhal R. Polycystic ovary syndrome and endometrial hyperplasia: An overview of the role of bariatric surgery in female fertility. Eur J Obstet Gynecol Reprod Biol 2016;207:220-6.  Back to cited text no. 48
    
49.
Christ JP, Falcone T. Bariatric surgery improves hyperandrogenism, menstrual irregularities, and metabolic dysfunction among women with polycystic ovary syndrome (PCOS). Obes Surg 2018;28:2171-7.  Back to cited text no. 49
    
50.
Skubleny D, Switzer NJ, Gill RS, Dykstra M, Shi X, Sagle MA, et al. The impact of bariatric surgery on polycystic ovary syndrome: A systematic review and meta-analysis. Obes Surg 2016;26:169-76.  Back to cited text no. 50
    
51.
Zhao X, Jiang Y, Xi H, Chen L, Feng X. Exploration of the relationship between gut microbiota and polycystic ovary syndrome (PCOS): A review. Geburtshilfe Frauenheilkd 2020;80:161-71.  Back to cited text no. 51
    
52.
Xu W, Tang M, Wang J, Wang L. Identification of the active constituents and significant pathways of Cangfu Daotan Decoction for the treatment of PCOS based on network pharmacology. Evid Based Complement Alternat Med 2020;2020:4086864.  Back to cited text no. 52
    
53.
Satpute SS, Shelke VV, Khot DS. PCOS; Modern and Ayurveda review W.S.R. to complication and management of Bija Kosha Granthi. Himal J Health Sci 2020;5(4):50-3.  Back to cited text no. 53
    
54.
Dayani Siriwardene SA, Karunathilaka LP, Kodituwakku ND, Karunarathne YA. Clinical efficacy of Ayurveda treatment regimen on Subfertility with Poly Cystic Ovarian Syndrome (PCOS). Ayu 2010;31:24-7.  Back to cited text no. 54
    
55.
Improvement in Biochemical and Psychopathologies in Women Having PCOS through Yoga Combined with Herbal Detoxification – ProQuest. Available from: https://www.proquest.com/openview/c425807a92d7f9d4308e0e1007eccf89/1?pq-origsite=gscholar&cbl= 2034826. [Last accessed on 2022 Mar 01].  Back to cited text no. 55
    
56.
Tomar S. Polycystic ovarian disease (PCOD) – Calcarea carbonica patient. Allgemeine Homöopathische Zeitung 2017;262(02):2-76. Available from: http://www.thieme-connect.de /DOI/DOI?10.1055 /s-0037-1601221. [Last accessed on 2022 Mar 01].  Back to cited text no. 56
    
57.
Rocha AL, Faria LC, Guimarães TC, Moreira GV, Cândido AL, Couto CA, et al. Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: Systematic review and meta-analysis. J Endocrinol Invest 2017;40:1279-88.  Back to cited text no. 57
    
58.
Stewart CE, Sohrabji F. Gonadal hormones and stroke risk: PCOS as a case study. Front Neuroendocrinol 2020;58:100853.  Back to cited text no. 58
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Pathophysiology
Risk Factors for...
Polycystic Ovary...
Diagnosis
Management: Life...
Management: Phar...
Management: Surgical
Management: Othe...
Complications
Conclusions
References

 Article Access Statistics
    Viewed204    
    Printed2    
    Emailed0    
    PDF Downloaded30    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]