Integrative machine learning models to unravel gut microbial dysbiosis and functional disruption in polycystic ovary syndrome.

Polycystic Ovarian Syndrome (PCOS) is a prevalent reproductive endocrinopathy which presents a significant clinical and public health problem (Morgante et al. 2015). PCOS can affect females throughout their lifespan leading to serious complications such as obesity, infertility, type two diabetes mellitus and cardiovascular disease (De Leo et al. 2016). The conventional approach to treating PCOS is guided by what symptoms affect the patient most such as infertility, hirsutism, acne and so forth. Many of the conventional treatments for PCOS such as metformin, anti-androgens and oral contraceptives can cause harmful adverse side-effects (Lamba et al 2018:65). Adverse side-effects, complications, dissatisfaction in various aspects of the patient- practitioner experience and failed therapies are among the main reasons that patients opt for Complementary and Alternative Medicine (CAM) therapy. CAM fulfils the expectations not met by conventional medicine, particularly the psychological impact of PCOS on patients, which are assessed by only a few conventional practitioners (Fauser et al. 2012). Aim of the study This study aimed to document existing therapeutic protocols in the management of PCOS from diagnosis to treatment used by practitioners within various disciplines of CAM in the context of their unique philosophical background. Furthermore, this information may be valuable in bridging any potential gap in information across the five CAM modalities investigated in this research with regards to PCOS. These modalities were: homoeopathy, Ayurveda (AV), Unani Tibb (UT), Traditional Chinese Medicine (TCM) and naturopathy. Methodology A qualitative approach was used to document the perceptions and protocols used in the diagnosis and management of PCOS by practitioners of the five selected CAM v modalities practicing within the boundaries of the eThekwini municipality. Stratified purposive sampling was implemented in order to select a sample frame of 12 participants. Data was collected by means of personalised, semi-structured interviews and the data collected was analysed using Tesch’s (Tesch 1990:329) and Creswell’s (Creswell 2014) methods. Results CAM philosophies are underpinned by the principles of innate healing, an individualised constitution and governing factors which manage homeostasis. TCM philosophy is guided by the yin and yang concept, homoeopathy by the vital force and miasms, AV by three doshas. UT by four humours and naturopathy by lifestyle factors. PCOS patients were generally classified as being sycotic and/or cancerinic (miasmatically) according to homoeopathy, having a melancholic, sanguineous temperament according to UT, presenting with excessive kapha and vata according to Ayurveda and a predominant yang deficiency with heat and moisture according to TCM. PCOS is a multi-faceted reproductive endocrinopathy which requires extensive management. The different roles of a family physician, endocrinologist, dermatologist, dietitian and gynaecologist in the diagnosis and holistic management of PCOS is performed collectively by a CAM practitioner. PCOS is considered an affliction of the woman and not merely as a disease of the ovaries and therefore much attention is drawn to the emotional drivers, particularly stress and abuse which affect these patients’ quality of life (QoL). Diagnostics reported by participants included: 1) A clinical diagnosis congruent with established diagnostic criteria such as the Rotterdam criteria which identified the pathognomonic features of PCOS and 2) A CAM-specific diagnosis which evaluated the entirety of the patient’s symptoms, emotions and characteristics in order to determine a constitutional weakness. vi This study found that management of PCOS, according to CAM participants, was aimed at correcting hormonal, ovulatory and menstrual imbalances, improving fertility, reducing obesity, managing infertility and improving the patient’s QoL. Management strategies generally comprised: 1) CAM-specific therapy which included medicines and/or procedures, 2) Adjunctive therapy which included supplements and the use of other modalities and 3) Lifestyle intervention which included dietary counselling, physical activity recommendations and emotional counselling. Conclusion In conclusion, PCOS is a multi-faceted condition which requires emotional support concomitantly with therapeutic support due to the clinical spectrum of changes that can have an impact on females’ psychological health.

Can shear wave elastography be used as a diagnostic marker in polycystic ovary syndrome?

The role of vitamin D in polycystic ovary syndrome

Low-Density Lipoprotein Receptor - Related Protein 5 (LRP 5) C/T Polymorphism in the Exon 18 in Polycystic Ovary Syndrome

36. Primary Care Provider Behaviors, Attitudes and Beliefs In the Diagnosis and Management of Polycystic Ovary Syndrome in Adolescents

To harmonise the diagnostic processes of polycystic ovary syndrome (PCOS) and enable clinicians to provide better patient care, it is critical to understand the knowledge gaps in PCOS diagnosis. We evaluated how clinicians in endocrinology, family medicine, general practice and gynaecology diagnose PCOS. This cross-sectional survey involved 208 clinicians from specific subspecialties across various healthcare settings in Singapore. A total of 160 responses were included in the final analysis. Among all the diagnostic criteria, the Rotterdam 2003 criteria was most frequently used (66.3%). More than half of the gynaecologists reported having a standardised workplace protocol while the majority from other specialties reported otherwise. A large percentage of respondents (60.5%) were unable to identify the correct PCOS clinical features, which is concerning. Only 8.8% of respondents used clinical and biochemical hyperandrogenism, menstrual disturbances and pelvic ultrasound to diagnose PCOS without performing unnecessary and incorrect investigations. Most clinicians recognised insulin resistance/type 2 diabetes mellitus and fertility problems as complications while only a few recognised psychological complications. Many clinicians (37.3%) sought standardisation of PCOS diagnosis and management guidelines for improvement in PCOS care and 81.9% of respondents would appreciate standardised educational materials. This is the first study to the best of our knowledge that gives an insight into the diagnostic and management processes of PCOS among various healthcare institutions in Singapore. This study calls for greater harmonisation of diagnostic processes and holistic evidence-based management of patients with PCOS through standardised workplace protocols and patient education resources.

New insights into the complex disease of PCOS: findings from early trophoblast invasion and placentation

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

Do contraception use, pregnancy outcome and number of children differ in women with and without polycystic ovary syndrome (PCOS)? Women with PCOS were less likely to report use of contraception and more likely to report a miscarriage, whilst number of children was similar between groups. The oral contraceptive pill is used in the management of PCOS, but the patterns of contraception use in women with PCOS is not known. In women with PCOS who undergo assisted reproduction, the risk of pregnancy loss appears higher, yet pregnancy loss and family size among community-based women with PCOS is not known. This is a cross-sectional analysis of a longitudinal cohort study. Mailed survey data were collected at five time points (years 1996, 2000, 2003, 2006 and 2009). Data from respondents to Survey 4 (2006), aged 28-33 (n = 9145, 62% of the original cohort aged 18-23 years) were analysed. This study was conducted in a general community setting. Data from participants who responded to the questions on PCOS, contraception and pregnancy outcome were analysed. The main outcome measures were self-reported PCOS, body mass index (BMI), contraception use, pregnancy loss and number of children. In women aged 28-33 years, women with PCOS were less likely to be using contraception (61 versus 79%, P < 0.001) and more likely to be trying to conceive (56 versus 45%, P < 0.001), compared with women not reporting PCOS. A greater proportion of women with PCOS reported pregnancy loss (20 versus 15%, P = 0.003). PCOS was not independently associated with pregnancy loss; however, BMI was independently associated with pregnancy loss in the overweight and obese groups (OR 1.2, 95% CI 1.04-1.4, P = 0.02 and OR 1.4, 95% CI 1.1-1.6, P = 0.001, respectively). Fertility treatment use was also independently associated with pregnancy loss (adjusted OR 3.2, 95% CI 2.4-4.2, P < 0.001). There was no significant difference in number of children between women with and without PCOS. PCOS, contraception use and pregnancy outcome data were self-reported. Attrition occurred, but is reasonable compared with similar longitudinal cohort studies. This community-based cohort aged 28-33 years provides insights into the contraceptive use, pregnancy loss and family size of a large cohort of unselected women. Women reporting PCOS had lower rates of contraception use and were more likely to be currently trying to conceive, suggesting that they may be aware of potential fertility challenges, yet in those not planning to conceive, contraceptive use was low and further education may be required. Despite prior reports of higher rates of pregnancy loss in PCOS, usually from infertility services, in this community-based population, PCOS was not independently associated with pregnancy loss, yet independent risk factors for pregnancy loss included higher BMI, were higher in PCOS. The number of children per woman was similar in the both groups, albeit with more infertility treatment in PCOS. This may reassure women with PCOS that with access to fertility treatment, family sizes appear similar to women not reporting PCOS.

Polycystic ovarian syndrome (PCOS), a lifestyle disorder that occurs due to hyperandrogenism in women. In this, FSH (follicle stimulating hormone) levels decrease whereas testosterone levels increase at once. There are many reasons for which PCOS occurs. Etiology and pathophysiology are discussed briefly in the present article. Aloe vera (Aloe barbadensis Mill.) is a renowned medicinal herb among the whole world for its pharmacological activities like ‘anti-diabetogenic’, ‘anti-microbial’, ‘anti-inflammatory’, ‘anti-obesity’ and clinical activities including ‘PCOS management’ and ‘wound healing’, ‘skin protection’ etc. The present paper objects to summarize the impact of aloe vera in PCOS management and other PCOS-induced disorders. It inhibits the genes that induce PCOS and aloe vera also regulates the activity of insulin. Several bioactive phytochemicals, present in aloe vera like ‘barbaloin’, ‘aloe-emodin-9-anthrone’, ‘lsobarbaloin’ ,’Anthrone-C-glycosides’ and ‘chromones’, ‘phytosterols’, ‘aloin’, ‘anthrone’, ‘aloe emodin’ , ‘aloetinic acid’ , ‘choline’ and ‘choline salicylate’ etc., which are responsible for its efficacy in PCOS and PCOS-induced disorders management.

Lower serum apelin levels in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a public and complex endocrine illness of female in their procreative ages. Females with PCOS take cluster of cardiac hazard features, such as overweightness, dyslipidemia, reduced glucose tolerance and high blood pressure. They are at high risk of emerging coronary heart disease (CHD). Fatty tissue theatres a dominant part in the association between cytokines and insulin resistance. The appearance of TNF-α and TNFR2 in fatty tissues is amplified in overweightness. TNF-α appearance associates with catalogs of insulin resistance and reductions with weightiness loss in equivalent with the development in insulin sensitivity. to evaluate the circulating concentrations of hs CRP, IL-6, IL-18 and TNF-α as serum markers of inflammation in a group of PCOS compared with healthy controls. This study included 120 patients who were carefully chosen from the case clinic of obstetrics and gynecology at Al-Hussein Hospital. Healthy Volunteers of age group 18- 45 years females with standard reproductive cycle were involved and those who current with history of inflammatory medications or illnesses are omitted. Patients who have high blood pressure or diabetes are also omitted from health control. The patients were alienated into three groups: Group 1: Healthy control, Group 2: Recently detected PCOS and Group 3: Previously on management for PCOS. There was statistically significant change between groups I with II and groups II with III regarding weight and BMI. There was statistically significant difference between groups I with II and I with III. There was statistically significant difference between three studied groups regarding LH, FSH and TSH. There was statistically significant difference between groups I with III and II with III. There was statistically significant difference between three studied groups regarding TNF-alpha. There was statistically significant difference between groups I with II and groups I with III. There was statistically significant difference between three groups studied regarding Hs-CRP. There was statistically significant difference between three studied groups regarding IL-18. There was significant negative correlation between IL-18 with IL-6, WHR (waist/hip ratio), FSH, and progesterone while there was significant positive correlation with Hs-CRP, WC (waist circumference), HC (hip circumference), LH and progesterone. The elevated plasma levels of TNF- α, IL-6 Hs-CRP and IL-18 among PCOS women reflects a state of chronic inflammation with potential implication for insulin resistance, independent of obesity.

Do circadian genes exhibit an altered profile in peripheral blood mononuclear cells (PBMCs) of polycystic ovary syndrome (PCOS) patients and do they have a potential role in androgen excess? Our findings revealed that an impaired circadian clock could hamper the regulation of peripheral steroid metabolism in PCOS women. PCOS patients exhibit features of metabolic syndrome. Circadian rhythm disruption is involved in the development of metabolic diseases and subfertility. An association between shift work and the incidence of PCOS in females was recently reported. This is a retrospective case-referent study in which peripheral blood samples were obtained from 101 control and 101 PCOS subjects. PCOS diagnoses were based on Rotterdam Consensus criteria. This study comprised 101 women with PCOS and 101 control volunteers, as well as Swiss albino mice treated with dehydroepiandrosterone (DHEA) to induce PCOS development. Gene expression analyses of circadian and steroidogenesis genes in human PBMC and mice ovaries and blood were executed by quantitative real-time PCR. We observed aberrant expression of peripheral circadian clock genes in PCOS, with a significant reduction in the core clock genes, circadian locomotor output cycles kaput (CLOCK) (P ≤ 0.00001), brain and muscle ARNT-like 1 (BMAL1) (P ≤ 0.00001) and NPAS2 (P ≤ 0.001), and upregulation of their negative feedback loop genes, CRY1 (P ≤ 0.00003), CRY2 (P ≤ 0.00006), PER1 (P ≤ 0.003), PER2 (P ≤ 0.002), DEC1 (P ≤ 0.0001) and DEC2 (P ≤ 0.00005). Transcript levels of an additional feedback loop regulating BMAL1 showed varied expression, with reduced RORA (P ≤ 0.008) and increased NR1D1 (P ≤ 0.02) in PCOS patients in comparison with the control group. We also demonstrated the expression pattern of clock genes in PBMCs of PCOS women at three different time points. PCOS patients also exhibited increased mRNA levels of steroidogenic enzymes like StAR (P ≤ 0.0005), CYP17A1 (P ≤ 0.005), SRD5A1 (P ≤ 0.00006) and SRD5A2 (P ≤ 0.009). Knockdown of CLOCK/BMAL1 in PBMCs resulted in a significant reduction in estradiol production, by reducing CYP19A1 and a significant increase in dihydrotestosterone production, by upregulating SRD5A1 and SRD5A2 in PBMCs. Our data also showed that CYP17A1 as a direct CLOCK-BMAL1 target in PBMCs. Phenotypic classification of PCOS subgroups showed a higher variation in expression of clock genes and steroidogenesis genes with phenotype A of PCOS. In alignment with the above results, altered expression of ovarian core clock genes (Clock, Bmal1 and Per2) was found in DHEA-treated PCOS mice. The expression of peripheral blood core clock genes in DHEA-induced PCOS mice was less robust and showed a loss of periodicity in comparison with that of control mice. N/A. We could not evaluate the circadian oscillation of clock genes and clock-controlled genes over a 24-h period in the peripheral blood of control versus PCOS subjects. Additionally, circadian genes in the ovaries of PCOS women could not be evaluated due to limitations in sample availability, hence we employed the androgen excess mouse model of PCOS for ovarian circadian assessment. Clock genes were assessed in the whole ovary of the androgen excess mouse model of PCOS rather than in granulosa cells, which is another limitation of the present work. Our observations suggest that the biological clock is one of the contributing factors in androgen excess in PCOS, owing to its potential role in modulating peripheral androgen metabolism. Considering the increasing prevalence of PCOS and the rising frequency of delayed circadian rhythms and insufficient sleep among women, our study emphasizes the potential in modulating circadian rhythm as an important strategy in PCOS management, and further research on this aspect is highly warranted. This work was supported by the RGCB-DBT Core Funds and a grant (#BT/PR29996/MED/97/472/2020) from the Department of Biotechnology (DBT), India, to M.L. B.S.J. was supported by a DST/INSPIRE Fellowship/2015/IF150361 and M.B.K. was supported by the Research Fellowship from Council of Scientific & Industrial Research (CSIR) (10.2(5)/2007(ii).E.U.II). The authors declare no competing interests. N/A.

The aim of the study was to identify differences in the level of anxiety, stress coping ways, personality traits, and social adjustments in infertile women with polycystic ovary syndrome (PCOS) compared to those without PCOS. In a case-control study, 257 infertile of women were recruited at Fatemeh Azahra Infertility and Reproductive Health Research Center (Babol, Iran) from May 2016 to December 2017. A total of 135 women with PCOS and 122 women without PCOS completed the following questionnaires; State-Trait Anxiety Inventory (STAI), Ways of Coping Questionnaire (WCQ), NEO Five-Factor Inventory (NEO-FFI), and Bell's Adjustment Inventory. Infertile women with PCOS had a higher mean score of trait anxiety than those without PCOS (46.19 ± 5.29 vs 44.49 ± 5.13, P = 0.004), but no difference was observed for state anxiety. The two groups did not have any significant differences in the mean scores of social adjustment and ways of coping, except for social support and problem-focused coping which were higher in the PCOS group. The PCOS personality traits of PCOS infertile women were not different regarding neuroticism, extraversion, agreeableness, conscientiousness. The only exception was that infertile PCOS women had a significantly higher mean score of openness to experience than those without PCOS (P = 0.049). Clinicians could take advantage of the psychological differences of infertile women with PCOS and without PCOS for better management of PCOS in infertility settings; despite higher levels of anxiety they are more likely to cope with stress and are welcome to new experiences.

STUDY QUESTIONWhat is the natural history of reproductive, psychological and oncological features in women with polycystic ovary syndrome (PCOS) in comparison to those without PCOS across the life course?SUMMARY ANSWERExisting longitudinal data on changes in reproductive, psychological and oncological features in PCOS are inadequate and conflicting, but the limited evidence suggests that total testosterone (T) and dehydroepiandrosterone sulphate (DHEAS) levels decline more significantly in women with PCOS than in those without PCOS, and the risk of gestational diabetes is higher in pregnant women with PCOS compared to their counterparts without PCOS.WHAT IS KNOWN ALREADYThe progression of reproductive, psychological and oncological features in PCOS remains unclear, which limits prevention and early diagnosis strategies across the lifespan. Understanding the natural history of PCOS is one of the overarching priorities in PCOS research.STUDY DESIGN, SIZE, DURATIONThis is a systematic review of longitudinal cohort studies with a narrative presentation of findings. Databases MEDLINE, EMBASE, Ovid PsycInfo, CINAHL PLUS and EBM reviews were searched between 15 January 2020 and 11 February 2021 with no language restrictions. Only studies published from the year 1990 to February 2021 were included.PARTICIPANTS/MATERIALS, SETTING, METHODSIn line with current guidelines for the assessment and management of PCOS, we included studies where participants were females with PCOS diagnosed according to the 2003 Rotterdam or the 1990 National Institutes of Health (NIH) consensus criteria.MAIN RESULTS AND THE ROLE OF CHANCEA total of 21 longitudinal studies including 62 123 participants over four continents reported reproductive, psychological and/or oncological outcomes. Participants were females aged between 15 and 49 years at baseline, with follow-up periods ranging from 4 weeks to 32 years. Consistent evidence based on limited studies suggests that total T and DHEAS levels decline to a greater degree in women with PCOS compared to those without PCOS, and the risk gestational diabetes is higher in women with PCOS than in those without PCOS. Evidence reporting changes over time in the majority of the remaining outcomes was unclear due to conflicting and/or insufficient information.LIMITATIONS, REASONS FOR CAUTIONThere was extreme heterogeneity between studies in terms of study setting, population characteristics, follow-up period, effect measures used and laboratory testing approaches.WIDER IMPLICATIONS OF THE FINDINGSUnderstanding the natural history of PCOS and changes in diagnostic, reproductive, psychological and oncological features of PCOS across the lifespan is still a challenge and the existing literature is both limited and conflicting. It is important that future long-term prospective longitudinal studies are conducted in unselected and well-characterized populations.STUDY FUNDING/COMPETING INTEREST(S)This specific study was not funded. S.K. is supported by scholarships from the Research Training Program of the Commonwealth of Australia and Monash University; H.J.T. is supported by an Australian National Health and Medical Research Council fellowship; and A.E.J. is supported by the Australian National Health and Medical Research Council's Centre for Research Excellence in Women’s Health in Reproductive Life. R.A. was employed by the American Society for Reproductive Medicine and is a consultant to Spruce Biosciences and Fortress Biotech. The other authors have no conflicts of interest to declare.REGISTRATION NUMBERProspero registration number: CRD42020165546.