BACKGROUND: Polycystic ovary syndrome (PCOS), a diagnosis of exclusion, is considered the most common endocrinopathy in females of reproductive age. Current cohorts of individuals with PCOS exist but are limited, specifically in racial/ethnic diversity, due to the complexity of multiple choice survey questions and difficulty to obtain data. METHODS: After examining existing cohorts and their questionnaires, an online survey was designed specifically to assess PCOS characteristics in a diverse population. The survey was field tested for cognitive understanding and usability in a diverse population, with respect to race/ethnicity and education. After cognitive testing, the survey was launched online and participants were recruited to complete the survey. Survey completion rates by level of education, race/ethnicity, and birthplace were established by determining the proportion of participants in each subgroup to complete the entire survey. We also looked at the average percentage of the survey participants in each subgroup completed before discontinuing the survey. Univariate regression analyses were performed to evaluate these results. Question comprehension was determined by evaluating all survey questions by length and complexity. The survey question asking participants to report their typical menstrual cycle length (MCL) was selected to assess participants’ question comprehension. Responses that fell outside of the normal range for MCL were examined and those that may have been inaccurate were isolated. Level of education and birthplace reported by participants who may have responded to the MCL question inaccurately were noted and assessed collectively. RESULTS: Two-hundred and forty-eight participants, aged 18-53 years, began the survey between August 9, 2017 and October 23, 2017. Of these participants, 71.7% identified as White; 11.7% as Hispanic, Latina, or of Spanish Origin; 12.6% as Black or African American; 13.2% as other races/ethnicities; and 9.2% as more than one race/ethnicity. Of the participants with some high school education, a high school diploma, or a GED, 74% completed the entire survey; of those with some college education or a 2-year degree, 81% completed the entire survey; and of those with a 4-year college degree or more, 90% completed the entire survey. On average, participants with a high school education completed 86% of the survey before discontinuing; those with some college education completed 91% of the survey before discontinuing; and those with a college degree or more completed 95% of the survey before discontinuing. Of the participants who identified as White, 92% completed the entire survey; of those who identified as Hispanic, Latina, or of Spanish Origin, 68% completed the entire survey; and of those who identified as Black or African American, 70% completed the entire survey, with statistical significance (p = 0.002). On average, participants who identified as White completed 96% of the survey before discontinuing; those who identified as Hispanic, Latina, or of Spanish Origin completed 82% of the survey before discontinuing; and those who identified as Black or African American completed 86% of the survey before discontinuing, with statistical significance (p = 0.002). Of the participants who were born in the United States, 92% completed the entire survey, and of the participants who were not born in the United States, 66% completed the entire survey, with statistical significance (p < 0.0001). On average, participants who were born in the United States completed 96% of the survey before discontinuing and participants who were not born in the United States completed 81% of the survey before discontinuing, with statistical significance (p < 0.0001). When asked to report their typical MCL, 66 participants (28.1%) responded with irregular answers and 20 (8.5%) may have responded inaccurately. Of these 20 participants, 18 (90%) completed at least some amount of college and 16 (80%) were born in the United States. DISCUSSION: This pilot study succeeds in establishing a cohort that is more racially/ethnically diverse than existing cohorts of individuals with PCOS. In order to gather more information on the ways in which PCOS manifests across different groups, future recruitment efforts ought to be more targeted towards individuals belonging to different racial/ethnic groups and socioeconomic statuses. Additionally, the baseline survey and future modules can be made more accessible to diverse groups through language translation. Furthermore, the addition of a menstrual cycle tracker component to the survey may increase the accuracy of information on participants’ menstrual cycle patterns.

Female sheep exposed to excess testosterone (T) in utero display symptoms similar to those observed in women with polycystic ovarian syndrome (PCOS). Prenatal T-treated ewes display masculinized sexual behavior and increased food-reward seeking behavior. A neural substrate critical for these goal-directed behaviors is the dopaminergic system in the ventral tegmental area. We have recently shown that in adult ewes dopamine expression in the VTA is increased by prenatal T exposure. In this thesis, I tested the hypothesis that alterations of the VTA dopamine system by prenatal-T are caused via activation of androgen (AR) and/or insulin receptors (IR). Analysis of immunohistochemical staining shows an increase of tyrosine hydroxylase (TH) expression, AR, or IR, along with changes in co-expression of AR/TH and IR/TH. These changes were blocked or reversed by prenatal treatments with flutamide or rosiglitazone, or postnatal treatments with rosiglitazone or metformin, implicating AR and IR in alterations of the VTA

Background: Polycystic ovary syndrome (PCOS) affects 6-10% of women and has a range of impacts on women’s reproductive, psychological, metabolic, and cardiovascular health. A lifelong condition, symptoms of PCOS may start in adolescence and extend into post-menopause. Despite being such a pervasive disorder, with significant burden of disease for some women, it may be underrecognized within the medical and general communities. Recent studies suggest that women with PCOS may not be diagnosed early or receive appropriate guidance and information from physicians. Little is known about women’s experiences in Canada. This thesis explores experiences with diagnosis and management in Canada and assesses the barriers and facilitators women face while seeking care for their condition. Methods: Research questions were addressed using a multi-methods approach. Participants were recruited from online PCOS groups on Facebook, Reddit, and stand-alone PCOS forums. An online questionnaire measured participants’ time to diagnosis, number of doctors seen, and satisfaction with information provided. Descriptive statistics, Chi-square tests, Fisher’s exact tests, and Spearman’s rank correlations assessed characteristics of the sample and correlations between demographic factors and satisfaction measures. Twenty-five follow-up interviews were held over the phone to elicit greater richness of experiences. Qualitative data were analyzed using thematic analysis and the interpretive description framework. Results: The e-survey was completed by 296 women aged 18-60 with a self-reported diagnosis of PCOS. Approximately a third (34%) of respondents waited for more than 2 years before attaining a diagnosis and 41% saw 3 or more doctors. Most participants were dissatisfied with the information provided to them about PCOS (66%). Many did not receive any information about lifestyle management (42%) or medical therapy (28%). Barriers to diagnosis and management included lack of knowledge and/or concern in physicians. Women received insufficient information about PCOS implications (including mental health) at the diagnosis and subsequent visits. Few participants had physicians who were involved with PCOS management. Peri- and post-menopausal women especially lacked support and medical information on how to manage symptoms. Facilitators to diagnosis and management included self-education, self-advocation, and social support. Women identified a need for greater PCOS awareness in primary care physicians and the general community. Few women had heard of PCOS prior to their diagnosis. Conclusion: This thesis found delays to diagnoses and dissatisfaction in women around the care and information they received from doctors. Perceived lack of knowledge and engagement in physicians resulted in most barriers to diagnosis and management. Few participants had physicians whom they could rely upon for information and guidance. Greater awareness of PCOS is needed in the medical community, particularly in primary care. Women and girls may benefit from greater PCOS awareness early in life in health class at the elementary and/or secondary levels.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine dysfunction problems among women of the reproductive age, with a global prevalence of 4-20%, causing 430,000 associated DALYs. Initial treatment of PCOS is mainly focused on diet and exercise and, if left untreated, PCOS can lead to many complications including, but not limited to, diabetes, metabolic syndrome, cardiovascular disease and endometrial cancer. In India, one out of five women are found to have PCOS with the numbers increasing with every year, according to a 2015 study done by Metropolis Healthcare. Some studies done in other parts of the country have shown that there is very limited knowledge about PCOS. Currently there is no data about the knowledge, attitudes and practices about PCOS in Kerala, India, which is an area known to have the highest rates of diabetes in India as well as an area having a high rate of infertility. PROPOSED PROJECT AND SIGNIFICANCE: This study is proposed to assess the knowledge, attitudes and practices of PCOS among women of reproductive age (18-45 years) in urban and rural areas of Thrissur, Kerala, India. This will help in understanding if there are any barriers to treatment and highlight the best preventive measures, as well as treatment strategies in this population, that might reduce its health burden. CONCLUSION: This will be a pilot study assessing perceptions of PCOS in Kerala, India. If this study demonstrates a low understanding of PCOS as shown in other parts of India, this will provide help in understanding the reasons why the prevalences of PCOS as well as diabetes and infertility, are increasing in the state of Kerala.

No description available.

Thesis (MNutr)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The role of fructose restriction in addition to dietary modifications for weight loss and lifestyle improvement, on fertility outcome and other markers of metabolic syndrome, in obese women with polycystic ovarian syndrome (PCOS) Introduction: At the time at which the current study was undertaken no data, as yet, existed on whether restriction of fructose, while treating obese patients with PCOS for weight loss, improves the clinical symptoms and metabolic/anthropometric profile so as to promote fertility. Objectives: To evaluate the baseline intake of fructose, as well as the effect of restricting fructose intake from fruit and soft beverages to less than 20 g daily, as well as to provide guidelines for weight loss on anthropometric measurements, for improving subjective clinical symptoms, and for promoting fertility outcome in obese patients with PCOS, who seek to become fertile. Methods: The study was conducted in the Tygerberg Hospital Infertility Clinic, as an experimental cohort. Patients with a body mass index (BMI) higher than 27, seeking fertility after diagnosis with PCOS, were referred for dietary consultation, and followed up 3 monthly over 1 year. At each visit anthropometric measurements and a detailed dietary history were taken and a questionnaire for clinical symptoms was completed. Results: Baselinely, 86 patients were included in the study. Averages for weight and BMI were 99.8 ± 24.3 kg and 39.2 ± 8.7kg/m2, respectively. Average baseline daily fructose intake was 167 ± 116.8g. At baseline, significant relationships were shown between fructose intake and burning feet (ρ=0.02) and frequent waking (ρ=0.02), with a trend towards nightly eating (ρ=0.07). The dropout rate after visit 1 was 50%, with a further dropout of 41% after visit 2. After 3 visits (n=18), fructose intake significantly reduced (ρ=0.018), with the significant relationships with clinical symptoms having disappeared by visit 2. After 3 visits (n=18), both weight and BMI decreased significantly (ρ=0.017) and (ρ=0.019), respectively. Fructose was tested as a covariate to BMI, with high significance (ρ=0.006) in said population group. Conclusion: Dietary intervention to reduce fructose intake proved significant for weight loss and BMI after 3 visits. Reduced fructose intake was associated with reduced clinical symptoms. With fructose being a significant covariate to BMI, it can be concluded that fructose overconsumption could possibly contribute to both clinical symptoms and elevated BMI in said study population. / AFRIKAANSE OPSOMMING: Die rol wat die beperking van fruktose speel bykomend tot dieetaanpassings en lewenstylverbetering vir gewigsverlies by oorgewig vroue met polisistiese ovariële sindroom (PCOS) in die uitkoms van fertiliteit en ander merkers van metaboliese sindroom. Inleiding: Met die aanvang van hierdie studie was daar is geen data beskikbaar oor die invloed van die beperking van fruktose in die dieet van oorgewig pasiënte met PCOS wat vir gewigsverlies behandel word nie. Dit was ook nie bekend of laasgenoemde pasiënte se kliniese simptome en metaboliese/antropometriese profiel sou verbeter met die beperking van fruktose sodat fertiliteit by hierdie pasiënte terselfdertyd ook bevorder word nie. Doelwitte: Die evaluering van die aanvanklike inname van fruktose, sowel as die beperking van fruktose afkomstig van eetbare vrugte en versoete drankies en sap tot ’n inname van minder as 20 g daagliks, tesame met riglyne vir gewigsverlies. Die uitkoms hiervan is bepaal deur antropometriese metings, die verbetering in subjektiewe kliniese simptome en die fertiliteituitkoms by oorgewig pasiënte wat hulp met fertiliteit verlang. Metodes: Die studie het as ’n eksperimentele kohort by die Infertiliteitskliniek by Tygerberg Hospitaal plaasgevind. Pasiënte wat na diagnose met PCOS fertiliteitsbehandeling verlang het en ’n BMI hoër as 27 gehad het , is vir dieetbehandeling verwys en driemaandeliks oor ’n tydperk van een jaar opgevolg. Tydens elke besoek is antropometriese metings en ’n omvattende dieetgeskiedenis geneem en ’n vraelys oor kliniese simptome ingevul. Resultate: Aanvanklik is 86 pasiënte by die studie ingesluit. Gemiddeldes vir gewig en BMI was 99.8 ± 24.3 kg en 39.2 ± 8.7 kg/m2 respektiewelik. Gemiddelde aanvanklike daaglikse inname van fruktose was 167 ± 116.8 g. Oorspronklik het betekenisvolle verhoudings tussen fruktose en die volgende bestaan: brandvoete (ρ=0.02) en veelvuldige episodes van nagtelike wakkerheid (ρ=0.02), met ’n neiging na nagtelike etery (ρ=0.07). Die uitvalsyfer na een besoek was 50% met ’n verdere uitvalsyfer van 41% na die tweede besoek. Na drie besoeke (n=18) het sowel die gewig as die BMI betekenisvolle afname getoon (ρ= 0.017) en (ρ=0.019), respektiewelik. Fruktose is as ’n belangrike kovariant vir BMI (ρ= 0.006) vir hierdie populasiegroep geïdentifiseer. Gevolgtrekking: Dieetintervensie vir die vermindering van die inname van fruktose was beduidend vir gewigsverlies en afname in BMI na drie besoeke. Verminderde fruktose-inname het gelei tot die vermindering van kliniese simptome. Met fruktose as beduidende kovariant vir BMI kan die gevolgtrekking gemaak word dat die oor-inname van fruktose by hierdie studiepopulasie waarskynlik tot sowel kliniese simptome as BMI bygedra het.

Indiana University-Purdue University Indianapolis (IUPUI) / Polycystic kidney diseases (PKD) are genetic disorders characterized by fluid filled cysts in the kidney tubules and liver bile ducts. There are two forms of PKD, autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). The focus of the studies in this thesis has been on ADPKD. The disease progresses slowly and the fluid-filled cysts grow in size due to increased rates of cell proliferation and fluid secretion into the cyst lumen. The expanding cysts compromise the normal kidney function and result in a decrease of renal function to the point of end-stage renal failure in midlife. Cyst enlargement is due, at least in part, to chloride secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Currently therapy is limited to renal cyst aspiration, dialysis, and eventually renal transplantation after organ failure, thus it has critical to determine possible drug therapies for the treatment of PKD. Previous studies showed that cyst fluid caused a secretory response in cells lining the cysts. We hypothesized that once the cyst have expanded and become so large that they burst or leak, which could also occur due to renal injury or aging, the cyst fluid may stimulate additional cyst growth. Lysophosphatidic Acid (LPA) was determined to be the active component of human cyst fluid, and we investigated the LPA stimulated signaling pathway. Our data suggest that the LPA stimulates chloride and fluid secretion by a combination of CFTR and Calcium-Activated chloride channels (CaCC) and that the two channels may functionally be linked to each other. The secretion is not occurring through a cAMP stimulated pathway, and it is possible that TMEM16A, a CaCC, plays a larger role than previously expected. Previous studies demonstrated that PPARγ agonists, insulin sensitizing drugs used to treat diabetes, inhibit chloride secretion by the collecting duct principal cells by decreasing CFTR synthesis. It was logical therefore to considered PPARγ agonists as long-term treatment for PKD. The first preclinical studied showed that high (20 mg/kg BW) dose pioglitazone, a PPARγ agonist, inhibited cyst growth in the PCK rat model, a slow progressing model, of PKD. To continue to look at the effects of the PPARγ agonists another preclinical study was completed, which tested if there was a class action of PPARγ agonists and if a lower dose was effective in treating the cystic burden. Using the PCK rat model, and another PPARγ agonist, rosiglitazone, a 24 week study was completed using 3 doses (4, 0.4, and 0.04 mg/kg BW). 4 mg/kg BW rosiglitazone is analogous to 20 mg/kg BW pioglitazone. The data indicated that the rosiglitazone is effective in lowering the cystic burden, and importantly the low dose proved to be effective. An additional rat model, the W-WPK rapidly progressing model was used to determine efficacy across multiple models, and to determine if there was a way to track the progress of the disease in a manner analogous to that used in human patients. The animals were treated with pioglitazone using 2 doses (2 and 20 mg/kg BW), and were imaged using CT scans to track the progress of the disease. The data suggest that pioglitazone was not as effective in the W-WPK rat model as it was the PCK rat model. There was a trend however, that low dose PPARγ agonist was as effective ad high dose. Even more important, the CT scans proved to be an effective way to track the progress of the disease in animal models.

Résumé : Le syndrome des ovaires polykystiques (SOPK) affecte 6-10% des femmes en âge de procréer et est la principale cause d’infertilité anovulatoire. Cette condition est principalement caractérisée par une hyperandrogénie provenant des ovaires et des glandes surrénales. De plus en plus d’études, à la fois in vivo et in vitro, indiquent qu’une surexposition ovarienne en gras, de même que les mécanismes lipotoxiques subséquents pourraient causer l’hyperandrogénie chez ces femmes. Ainsi, cette étude vise à 1) évaluer l’implication des gras et de l’inflammation folliculaire dans la production des androgènes ovariens par une étude de corrélation; et 2) comparer les niveaux folliculaires de gras, métabolites lipidiques et marqueurs inflammatoires entre les femmes SOPK et non-SOPK. Cette étude transversale a recruté 80 femmes en cours de fécondation in vitro. Treize étaient SOPK, 58 étaient non-SOPK et 9 avaient un diagnostic incertain. Les participantes au projet avaient un âge moyen de 33 ± 4 ans. Tout groupe confondus, les niveaux folliculaires de testostérone corrélaient avec les gras (r=0,381; P=0,001; indépendamment de l’IL-6), les acylcarnitines (r≥0,255; tout P=0,008; non indépendamment des gras) et l’IL-6 (r=0,300; P=0,009; indépendamment des gras). De plus, les niveaux folliculaires de gras corrélaient avec les acylcarnitines (r≥0,594; tout P<0,001). Lorsque comparées aux femmes non-SOPK, les femmes SOPK étaient plus obèses (BMI: 31,2 vs. 25,1 kg/m2; P=0,009) et avaient des niveaux folliculaires plus élevés de testostérone (12,9 vs. 0,29 nM; P=0,001), de gras (P=0,001), d’acylcarnitines (tout P=0,001) et du marqueur inflammatoire IL-6 (13,0 vs. 8.6 pg/mL; P=0,018), le tout indépendamment de l’IMC. Les résultats suggèrent qu’une exposition intra-ovarienne en gras pourrait contribuer à une augmentation de la production des androgènes. Les mécanismes pourraient inclure une β-oxydation insuffisante, illustré par des acylcarnitines élevés, menant à l’accumulation de métabolites lipidiques toxiques, et une inflammation ovarienne, possiblement suite à une infiltration de macrophages. Ces deux mécanismes semblent être indépendants. De plus, l’environnement ovarien des femmes SOPK est caractérisé par une élévation des gras, de métabolites lipidiques et de marqueurs inflammatoires. Il peut donc être proposer que l’hyperandrogénie caractéristique du SOPK soit causée en partie par la lipotoxicité. // Abstract : Polycystic ovary syndrome (PCOS) affects 6-10% of the women of childbearing age and is the main cause of anovulatory infertility. It is mainly characterised by hyperandrogenism that can originate from the adrenal gland and the ovaries. A growing number of evidences, either in vivo or in vitro, points toward an overexposition to fat and lipotoxic mechanisms (lipid induced cellular toxicity) as the cause of PCOS hyperandrogenesis. Therefore, we aimed to: 1) evaluate the implication of follicular fluid (FF) levels of fat and inflammation markers in the ovarian production of androgens through a correlation analysis; and 2) compare FF levels of lipids, lipid metabolite levels and inflammation markers between PCOS and non-PCOS women. This cross-sectional controlled study was performed with 80 women undergoing an IVF procedure. Among them, 13 were PCOS, 58 were non-PCOS and 9 had an uncertain diagnosis. Participants were aged 33 ± 4 years old and had an average body mass index (BMI) of 25.7 ± 6.2. When analysing all women, follicular levels of testosterone correlated significantly with fat (NEFA + triglycerides) (r=0.381; P=0.001; independently of l’IL-6), acylcarnitines (r≥0.255; all P=0.008; not independently of fat) and l’IL-6 (r=0.300; P=0.009; independently of fat). Moreover, follicular levels of fat significantly correlated with acylcarnitines (r≥0.594; all P<0.001). When compared to non-PCOS women, PCOS women were significantly more obese (BMI: 31.2 vs. 25.1 kg/m2, P=0.009) and had significantly higher follicular levels of testosterone (12.9 vs. 0.29 nM, P=0.001), fat (P=0.001), acylcarnitines (all P=0.001) and inflammatory marker IL-6 (13.0 vs. 8.6 pg/mL, P=0.018), everything independently of BMI. Our results suggest that intra-ovarian exposure to fat may be responsible for the increased production of androgens. Mechanisms are likely to include an insufficient β-oxidation, leading to the accumulation of toxic lipid metabolites, and ovarian inflammation, possibly through macrophage infiltration. Both these mechanisms seem independent of one another. Also, intra-ovarian environment of PCOS women are characterized by increased levels of fat, acylcarnitines and inflammatory marker. It can thus be proposed that lipotoxic mechanisms are responsible for the increased production of androgen that is characteristic of PCOS women.

Το σύνδρομο πολυκυστικών ωοθηκών (PCOS) αποτελεί την πιο συχνή ενδοκρινολογική διαταραχή των γυναικών αναπαραγωγικής ηλικίας που χαρακτηρίζεται από κεντρικού τύπου παχυσαρκία, ακμή, υπερτρίχωση και διαταραχές των εμμηνορησιακών κύκλων που οφείλονται στην υπερανδρογοναιμία και την χρόνια ανωοθυλακιορρηξία. Οι γυναίκες με PCOS αναπτύσσουν και μεταβολικού τύπου διαταραχές όπως η υπερινσουλιναιμία λόγω αντίστασης στην ινσουλίνη, η υπέρταση, ο σακχαρώδης διαβήτης, η δυσλιπιδαιμία και το μεταβολικό σύνδρομο. Τα τελευταία χρόνια γίνονται πολλές γενετικές μελέτες προκειμένου να προσδιορισθούν οι μοριακοί γενετικοί μηχανισμοί που εμπλέκονται στην παθογένεια του ΣΠΩ. Ένας σημαντικός ρυθμιστής της ωοθυλακιογένεσης που πιθανόν να παίζει ρόλο στην παθοφυσιολογία του ΣΠΩ είναι η αντιμυλλεριανική ορμόνη (ΑΜΗ). Eντός του εξωνίου 1 του γονιδίου της ΑΜΗ εδράζεται ο πολυμορφισμός Ιle49Ser (ref SNPID:rs10407022) που συνίσταται στην αλλαγή μιας βάσης θυμίνης (T) από γουανίνη (G) δημιουργώντας τρεις γονότυπους: ομοζυγώτες GG, oμοζυγώτες TT, ετεροζυγώτες GT. Δεδομένου του ρόλου της ΑΜΗ στην παθοφυσιολογία του συνδρόμου των πολυκυστικών ωοθηκών αλλά και της ενδεχόμενης χρήσης της ως διαγνωστικό και προγνωστικό δείκτη του συνδρόμου, ο πολυμορφισμός Ιle49Ser έχει καταστεί αντικείμενο μελέτης. Στην παρούσα μελέτη προσδιορίστηκε ο πολυμορφισμός Ιle49Ser σε 111 γυναίκες με ΣΠΩ και 67 υγιείς μάρτυρες . Από τη στατιστική ανάλυση δεν προέκυψε κάποια στατιστικά σημαντική διαφορά στη συχνότητα των γονοτύπων του πολυμορφισμού Ile49Ser του γονιδίου της ΑΜΗ ανάμεσα στις γυναίκες με ΣΠΩ και του υγιούς πληθυσμού ελέγχου. Από τη στατιστική ανάλυση, επίσης, δεν προέκυψε συσχέτιση των γονοτύπων με κάποια από τις ορμονικές ή κλινικές παραμέτρους των γυναικών με ΣΠΩ. Η απουσία συσχέτισης του πολυμορφισμού Ile49Ser με αυξημένο κίνδυνο για ΣΠΩ δείχνει ότι το σηματοδοτικό μονοπάτι της ΑΜΗ εμπλέκεται στην παθογένεια του συνδρόμου με έναν έμμεσο τρόπο. Ωστόσο περισσότερες μελέτες είναι απαραίτητες προκειμένου να διαλευκανθεί ο ρόλος της ΑΜΗ στην ανθρώπινη ωοθυλακιογένεση, όπως και στην παθοφυσιολογία του συνδρόμου των πολυκυστικών ωοθηκών. / The polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age, characterized by central obesity, acne, hirsutism and disorders of menstrual cycles due to hyperandrogonemia and chronic anovulation. Women with PCOS develop type and metabolic disorders such as hyperinsulinemia due to insulin resistance, hypertension, diabetes mellitus, dyslipidemia and metabolic syndrome. Over the last decade there are an increasing number of studies conducted in order to identify the molecular genetic mechanisms that are involved in the pathogenesis of PCOS. AMH seems to be an important regulator of follicle development and may also play a significant role in the pathogenesis of PCOS. The polymorphism Ile49Ser (ref SNPID:rs10407022) is located in exon 1 of AMH gene and results from the conversion of thymine (T) to guanine (G) giving three genotypes: homozygotes TT, GG and heterozygotes GT. Taken as granted the role of AMH in the pathophysiology of PCOS and the possible use of AMH levels as a diagnostic and prognostic marker of the syndrome, recent studies concern the involvement of IIe49Ser polymorphism. The precent study identified the polymorphism Ile49Ser in a cohort of 111 women with PCOS and 67 controls. Genotype frequencies for the AMH Ile49Ser polymorphism were similar in PCOS women and controls. In addition, AMH Ile49 Ser variant was not associated with clinical or hormonal parameters of PCOS women. The absence of an association of AMH Ile49Ser polymorphism with susceptibility to PCOS indicates that the AMH signaling pathway is not directly involved in the pathophysiology of PCOS. More studies should be carried out in order to determine the role of AMH in human ovarian physiology.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is an endocrine disrupting disorder affecting at least 10 percent of reproductive-aged women. In many cases, women develop comorbidities such as diabetes, cardiovascular disease, and other metabolic disorders. In North America and Europe, it takes several years and multiple doctors for women to receive a diagnosis of PCOS. This results in lost time for risk-reducing interventions. Menstrual tracking applications are one potential tool to alert women of their risk for PCOS and prompt them to seek further evaluation from a medical professional. OBJECTIVE: The objective was to develop the Irregular Cycles Feature (ICF) on the mobile phone application Clue®, which generates a probability of a user’s risk for PCOS. The secondary aim was to assess the accuracy of the tool by testing the feature on virtual test subjects. METHODS: A literature review was conducted to generate a list of signs and symptoms of PCOS. Probabilities were assigned to each variable and built into a Bayesian Network. The Irregular Cycles Feature, an adaptive questionnaire, was then developed in order to detect high-risk PCOS patients. The ICF detected at risk Clue® users through self-reported menstrual cycles and answers to medical history questions. Upon completion of the questionnaire, a Result Screen is displayed to the user. The Screen is a summary of the individual’s probability of having PCOS. For each eligible user, a Doctor’s Report is also generated. This is a screen containing information regarding menstrual irregularities and a brief medical history to be used by a medical professional in order to make a final diagnosis. Both the Result Screen and Doctor’s Report disclose information about PCOS and detailed explanations for consulting a medical provider. A brief statistical validation was then performed to compare the output of the network to predictions made by a physician-scientist using a correlation coefficient, a p-value, and a Pearson’s coefficient. RESULTS: The Irregular Cycles Feature successfully predicts probability of PCOS based on eight test cases. The correlation between the network’s calculation and the assessment made by a board-certified reproductive endocrinology/infertility physician-scientist was 0.82, with a p-value of less than 0.05. The Pearson’s coefficient was calculated to be 0.69. These values indicate that the ICF made statistically significant predictions when compared to the physician-scientist. CONCLUSIONS: The ICF provides consumer-friendly ways to improve interactions between medical providers and patients. The tool can be adapted to capture other causes of menstrual irregularities and can serve as an important mechanism for drawing attention to potentially hazardous health problems. Further validation studies will be conducted to confirm the utility of the ICF with Clue® users, particularly amongst those who receive an official diagnosis from a medical professional. / 2020-06-17T00:00:00Z