Educational Program: Its Effect on Knowledge and Lifestyles among Paramedical Students with Polycystic Ovarian Syndrome (PCOS)

Periodontal disease in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), also known as Stein-Leventhal Syndrome, was first described in 1935. PCOS, which may also be referred to as polycystic ovary disease is the most common hormonal disorder found in premenopausal women. PCOS is the most common endocrine disorder in women of reproductive age and is the most common cause of infertility due to ovulation. A PCOS is an endocrine disorder which affects the adolescent girls. A PCOS is a condition in which a woman has an imbalance of female sex hormones. This may lead to changes in the menstrual cycle, cyst in the ovary, failure to conceive, and other health problems. It is a common health problem among teenagers and young women. It affects 5–10% of women in their reproductive years. These problems cause infertility. Two principal components to diagnose this syndrome are menstrual dysfunction and clinical or laboratory hyperandrogenism in which these items are used in clinical diagnosis. PCOS is a hormonal disorder that affects between 5% and 10% of women of reproductive age and remains the most enigmatic reproductive disorders. The most common symptoms of PCOS are obesity, acne, amenorrhea, irregular menstrual cycles, hirsutism, insulin resistance (IR), and high cholesterol. Due to the varied nature of PCOS and the large range of possible signs and symptoms, health personnel need a thorough knowledge of the disorder and its management. It is a major disorder characterized by elevated levels of male hormones (androgens), acne, and hirsutism. It can even cause IR, anovulation, and infertility on prolonging incidence of cysts. One of the treatments for PCOS is the use of synthetic medicine, which can help to treat PCOS but with side effects. However, many women who suffer from PCOS opt to use alternative medicine in conjunction with traditional medicine to improve their condition. There are some herbs that are very helpful in treating PCOS. Since PCOS is a curable disorder, it can be cured by the use of natural remedies or allopathic medication. There is a growing interest in herbal remedies or allopathic medication to cure the PCOS. There is a need to change the lifestyle management, diet to control the PCOS level. The natural remedies include treatment with phytoestrogenic and non-estrogenic herbs such as Licorice, Ginseng, Black cohosh, Dong, soy, evening primrose, honey, fenugreek, Schisandra root, and many other which are effective and safe. Many plants have been highly esteemed sources and have advantages which reduce PCOS and also having a hypoglycemic effect. In this review, an attempt has been made to study the use of natural remedy for the treatment of PCOS.

Circulating levels of anti-Mullerian hormone (AMH) have significantly increased in adolescent girls with polycystic ovary syndrome (PCOS) compared with that of normal girls. This is consistent with findings in adult PCOS and normal women. Previous studies in both adolescent girls and women with PCOS have shown a close correlation of circulating AMH levels to the antral follicle count, and it has been proposed that serum AMH may be a useful biological marker for the presence of PCOS. Adolescent girls with oligomenorrhea (OLIGO) without evidence of hyperandrogenism may show increased pulsatile LH secretion similar to girls with PCOS. Without ovarian imaging studies and in the absence of hyperandrogenism, it is unclear whether girls with OLIGO fulfill the criteria for diagnosis of PCOS. A finding of elevated AMH serum levels in adolescent girls with OLIGO would be strongly suggestive of PCOS. No studies are available comparing serum AMH concentrations among adolescent girls with PCOS or OLIGO without evidence of hyperandrogenism. This prospective study compared serum AMH levels in adolescent girls with OLIGO, PCOS, or regular menstrual cycles (normal controls). The comparison groups were comprised of 24 girls with OLIGO who had no evidence of hyperandrogenism, 153 girls with PCOS, and 39 normal controls, as well as 73 women with PCOS, and 36 normal adult women. Baseline blood samples were drawn on an arbitrary day in girls with OLIGO and PCOS, and from the early to mid-follicular phase of the menstrual cycle in adolescent normal controls. Blood samples were obtained similarly in adult women. There was no significant difference in the basal serum AMH levels of adolescent girls with OLIGO (5.33 ± 0.47 ng/mL) or PCOS (5.28 ± 0.26 ng/mL) girls or PCOS adults (6.36 ± 0.47 ng/mL). Similarly, there was no significant difference between normal control adolescents (3.05 ± 0.31 ng/mL) and normal control adults (2.33 ± 0.22 ng/mL). AMH levels were significantly lower among obese adolescents and PCOS women compared with lean controls (P < 0.02 for each comparison). These findings suggest that adolescent girls with OLIGO have elevated antral follicle number similar to adolescents with PCOS, which is suggestive for diagnosis of PCOS.

Increased monocyte chemoattractant protein-1 levels indicating early vascular damage in lean young PCOS patients

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, affecting 4.8 % to 18.6 % of women of reproductive age. Between 10 and 19 years of age, PCOS occurs in 3.39 % to 8.03 % of adolescents. Confirmation of diagnosis in adolescent age is difficult because manifestations of PCOS are similar to normal puberty signs (e. g., irregular menstrual cycle, acne, etc.). New evidence-based guidelines have been issued in 2018 highlighting the diagnostic criteria for establishing PCOS diagnosis in adolescents. These guidelines also recommend a separate identification of risk group patients – adolescent patients for whom both diagnostic PCOS criteria have not yet been confirmed and who should continue to be monitored. It is important to diagnose this disease as early as possible in order to initiate lifestyle adjustments and possibly also begin treatment in a timely manner.In the long term, PCOS increases the risk of developing infertility and type 2 diabetes, cardiovascular disease, insulin resistance and metabolic syndrome. Increased body weight occurring in 40–70 % of adolescents with PCOS significantly increases the risk of chronic non-communicable diseases at a later stage, and maintains PCOS symptoms. PCOS and associated symptoms reduce health-related quality of life (HRQOL). Binge eating is more common in patients with PCOS. The most effective tactics of therapy are lifestyle changes, so it is particularly important to recognise patients at increased risk of developing PCOS, to diagnose them early and to offer treatment that is most relevant to the needs of the individual and improves their quality of life.The aim of the doctoral thesis is to explore intergenerational, genetic, quality of life and binge eating aspects in teenagers with PCOS.The study contains several sections. To evaluate the intergenerational bond, 57 teenagers with PCOS and their mothers were included in Section I. The section studies the relationship between patients with PCOS and their mothers. In addition to PCOS patients, Section II also includes healthy adolescent patients and patients at risk. The role of the most common variation of protein-coding genes involved in the activity of the Hypothalamic-Pituitary-Ovarian axis (FSHR, ESR2, LHCGR, GNRHR) in PCOS development and in the PCOS clinical presentation was studied by including 63 adolescents with a diagnosis of PCOS, 67 healthy control patients and 22 patients at risk. The role of CYP21A2 gene variations in PCOS development and clinical phenotype was established in 55 PCOS patients, 49 control patients and 23 patients at risk. Additionally, components of HRQOL, binge eating and factors affecting the total HRQOL were analysed in 63 PCOS patients and 66 control patients. The study concluded that it was not possible to predict clinical symptoms associated with PCOS in adolescents based on PCOS symptoms in their mothers. The role of protein-coding gene variations that are involved in the functioning of sex hormones was also not found, in regard to PCOS development. However, it was found that the homozygous minor allele carriers within variations of specific genes (ESR2 rs4986938 and LHCGR rs2293275) had a higher total testosterone level in blood than patients who were not carriers of these alleles. The most important components that affected HRQOL in adolescents with PCOS were the diagnosis of PCOS as such, the degree of binge eating, and the percentile of the body mass index. At the same time, HRQOL was most affected by concerns about body hair and body weight. There was no difference in the frequency of binge eating between PCOS patients and adolescent control group patients.In this study, no link was found between the diagnosis of PCOS or associated symptoms in mothers and the phenotype of adolescents with PCOS. Individual alleles have been associated with the clinical presentation of PCOS. There is a better understanding of the components of HRQOL that affect PCOS the most and require particular attention in clinical practice. Further research with a larger sample-size is needed. Furthermore, longitudinal data on the population studied in this project would provide a more accurate insight into the development of the disease at a later age.

PCOSt: A non-invasive and cost-effective screening tool for polycystic ovary syndrome

Objective To evaluate the change of expression of estrogen receptor(ER) and progesterone receptor(PR) in endometrium of polycystic ovarian syndrome(PCOS) patients during induced ovulation and its clinical significance.Methods We recruited 108 PCOS patients as the disease group and 96 women with tubal infertility as the normal control group.Both groups were randomly divided into three groups with equal numbers (metaphase of generation group,metaphase of secretion group and ovulation group) and were tested the change of ER and PR levels in endometrium of PCOS patients at the fifth day after menstruation,ovulation period and the seventh day after ovulation with way of immunohistochemistry.Results There was marked change of ER and PR in the menstrual cycle of healthy controls.The levels of ER and PR were (0.89 ± 0.22) kU/L and (0.72 ±0.25) kU/L,and (1.65 ± 0.42) kU/L and (1.43 ± 0.42) kU/L respectively at metaphase of generation and (0.92 ± 0.29) kU/Land (0.87 ± 0.34) kU/L,and (1.68 ± 0.42) kU/L and (1.56 ± 0.30) kU/L respectively at metaphase of secretion.Positive gland decreased significantly during ovulation period (ER:(0.69 ± 0.35) kU/L and (0.55 ± 0.24) kU/L; PR:(0.97 ± 0.32) kU/L and (0.69 ± 0.30) kU/L).The levels of ER of stroma and positive gland in menstruation of PCOS patients were significantly higher than in menstruation of normal women during all the stages of menstrual cycle and did not have non-linear change (Metaphase of generation:(1.73 ± 0.22) kU/L and (1.89 ± 0.38) kU/L; Ovulation:(0.75 ± 0.32) kU/L and (0.63 ± 0.28) kU/L;Metaphase of secretion:(1.79 ± 0.31) kU/L and (1.90 ± 0.30) kU/L).The levels of PR in menstruation of PCOS patients were significantly lower than in menstruation of normal women during all stages of menstrual cycle (P ＜ 0.05).We did not observe trend of elevation of PR levels in PCOS patients (Metaphase of generation:(0.93 ±0.36) kU/L and (0.85 ± 0.56) kU/L; Ovulation:(0.77 ± 0.26) kU/L and (0.56 ± 0.41) kU/L) ;Metaphase of secretion:(0.98 ±0.36)kU/L and (0.88 ±0.47)kU/L).Conclusion The expressions of ER and PR in endometrium of PCOS patients are abnormal during all stages of induced ovulation.The endometrial receptivity of PCOS patients is worse than normal women.Improving the receptivity of ER and PR of PCOS patients is one of the ways to enhance pregnancy of PCOS patients. Key words: Polycystic ovarian syndrome; Ovulation period; Estrogen receptor

Determination of the best-fitting ultrasound formulaic method for ovarian volume measurement in women with polycystic ovary syndrome

STUDY QUESTIONDoes ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)?SUMMARY ANSWERIncreased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation.WHAT IS KNOWN ALREADYProgrammed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear.STUDY DESIGN, SIZE, DURATIONFerroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6–16) and PCOS (n = 7–18) patients. The experimental study was completed in vitro using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group).PARTICIPANTS/MATERIALS, SETTING, METHODSOvarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored in vivo in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed.MAIN RESULTS AND THE ROLE OF CHANCEIncreased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe2+ (P < 0.05) and MDA (P < 0.05), and upregulated nuclear receptor coactivator 4 protein levels, and downregulated ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) proteins were observed in the hGCs in patients with PCOS and ovaries of PCOS rats (P < 0.05 versus control). DHT was shown to induce ferroptosis via activation of NOCA4-dependent ferritinophagy. The inhibition of ferroptosis with Fer-1 in rats ameliorated a cluster of PCOS traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality (P < 0.05). Treating rats with RSL3 resulted in polycystic ovaries and hyperandrogenism (P < 0.05).LARGE-SCALE DATAN/A.LIMITATIONS, REASONS FOR CAUTIONAlthough ovarian-targeted ferroptosis inhibition may be a more targeted treatment for PCOS, the underlying mechanisms in the cycle between ferroptosis and hyperandrogenism require further exploration. Additionally, since PCOS shows high heterogeneity, it is important to investigate whether ferroptosis increases are present in all patients with PCOS.WIDER IMPLICATIONS OF THE FINDINGSAndrogen-induced ovarian ferroptosis appears to play a role in the pathogenesis of PCOS, which potentially makes it a promising treatment target in PCOS.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by the National Key R&D Program of China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), National Natural Science Foundation of China (No. 82130046, 82320108009, 82101708, 82101747, and 82001517), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (No. SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003) and Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (No. 20161413), Shanghai’s Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors report no competing interests.

Disclosure: Y.G. Rivera-Rodriguez: None. B. Diaz Rios: None. C.M. Casas Loyola: None. B. Marin Rodriguez: None. P.A. Alicea Reyes: None. J. Romaguera: None. L.A. Gonzalez-Rodriguez: Research Investigator; Self; Eli Lilly &amp; Company. Purpose: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting women across their lifespan, with metabolic complications that are often overlooked. Studies have revealed an inadequate understanding of PCOS, its complications, and management. There is also limited information about this condition in Hispanic women. The purpose of this study is to assess the knowledge about PCOS and its complications among a sample of Hispanic women living in Puerto Rico. Methods: This is a descriptive cross-sectional study of Hispanic women aged 21-45 years recruited from the General Endocrinology and Gynecology Clinics at the UPR-RCM Clinics. A self-administered questionnaire assessing their knowledge about PCOS, and its complications was given. Patients were classified according to PCOS diagnosis. Results were compared between the groups. Results: A total of 47 women were included in this study. Approximately 45% of participants had a diagnosis of PCOS. Most participants agreed that PCOS involves a set of symptoms associated with hormonal imbalances (94%) and irregular menses (91%). Only 40% of participants considered PCOS a chronic condition without a cure and only 34% acknowledge weight loss as one of the treatments of this condition. Two-thirds of participants didn’t know that PCOS can be diagnosed with blood tests. When assessing their knowledge about complications related to PCOS, we found that only 36% associated PCOS with an increased risk of cardiovascular disease, 56% with obesity and 62% with abnormal blood glucose levels. When comparing the knowledge about their condition in patients with a diagnosis of PCOS, we found increased knowledge about signs and symptoms such as hirsutism, hair loss and weight gain when compared to controls. However, when assessing their knowledge about complications related to PCOS, neither group recognized PCOS as a chronic condition, or associated PCOS with cardiovascular, metabolic complications and/or increased risk of cancer. Conclusion: Our study suggests that there is a lack of general knowledge about PCOS and its long-term complications among a sample of Hispanic women in reproductive years. Most importantly, our data showed that even patients with a diagnosis of PCOS do not understand their condition or comprehend the associated complications. Our study emphasizes the need to develop educational tools and strategies to improve the general population knowledge about this condition and raise awareness about preventable complications and the importance of early treatment. Presentation: 6/3/2024

Integrated ovary-specific DNA methylation profiling and transcriptome reveals novel regulatory features in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) affects around 15% of Indigenous women who are also a group at high risk of cardiometabolic disease. To explore the impact of PCOS on metabolic syndrome in Indigenous women. A cross-sectional reproductive health questionnaire, biochemical and anthropometric assessments, of 109 Indigenous women (35 with PCOS and 74 without PCOS) aged 15-44 years in and around Darwin between 2003 and 2005. PCOS was defined using the National Institutes of Health criteria, and metabolic syndrome (MetS) using the National Cholesterol Education Programme Adult Treatment Programme III criteria. The outcome was prevalence of MetS by PCOS status; relationship of PCOS with MetS before and after adjustment for markers of obesity and insulin resistance. Women with PCOS had a significantly higher body mass index (BMI) (P = 0.0001) and MetS was more frequent in women with PCOS (51%) than those without PCOS (23%) (P = 0.003). The most frequent components of MetS in both groups were a high density lipoprotein cholesterol ≤1.29 mmol/L (80% PCOS, 55% non-PCOS) and a waist circumference >88 cm (77% PCOS, 41% non-PCOS); these were significantly more frequent in women with PCOS (P = 0.01). In logistic regression models, PCOS was significantly associated with MetS by itself but not after adjustment for BMI or sex hormone binding globulin. While MetS was more common in Indigenous women with PCOS, PCOS was not an independent predictor of MetS. This may be because obesity and insulin resistance are integral parts of PCOS and are the mechanisms through which PCOS exerts metabolic effects.

Anti-Mullerian-hormone (AMH) does not seem to fluctuate significantly during the menstrual cycle in healthy women. However, little is known about cycle fluctuations of AMH levels in patients with polycystic ovarian syndrome (PCOS). The purpose of this study was to examine AMH fluctuations during the follicular phase in PCOS patients receiving antiestrogens or recombinant follicle-stimulating hormone (FSH). About 40 PCOS patients diagnosed according to Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 19 controls were prospectively enrolled. PCOS patients received either antiestrogens or recombinant FSH for monoovulation induction and controls received antiestrogens. AMH levels were determined (1) between the 2nd and the 5th day of follicular phase and (2) when a single large dominant follicle ≥18 mm had appeared. Our study shows that AMH levels do not change during follicular development in controls as well as in PCOS patients with AMH levels < 5 ng/ml, irrespective of antiestrogen or FSH therapy. However, in PCOS patients with AMH levels ≥5 ng/ml, AMH declines significantly during follicular development (p < 0.01). We conclude that AMH levels should be determined in the early follicular phase in PCOS patients without the influence of antiestrogens or exogenous FSH, because these interventions may lower AMH values in patients with high levels.

Serum testosterone levels decrease in middle age in women with the polycystic ovary syndrome

BackgroundA diagnosis of Polycystic Ovary Syndrome (PCOS) and its related phenotypic features including increased hair growth can affect a woman’s social and emotional well-being. We aim to determine firstly, if excess body weight affects menstrual cycle length, excessive hair growth and other phenotypic features in healthy women without PCOS and secondly, whether having PCOS exacerbates the effects of high body mass index (BMI).MethodsA prospective cross-sectional study involving healthy women (21–45 years) recruited at an annual health screen for hospital staff and volunteers from the university community, and PCOS cases referred to tertiary gynecological clinics in Singapore. To dissect the independent and/or combinatorial effects of PCOS and BMI on the phenotypic features, subjects were divided into four categories: non-PCOS (normal BMI), non-PCOS (high BMI), PCOS (normal BMI), and PCOS (high BMI). General linear modelling was performed to compare clinical, ovarian, hormonal and metabolic parameters across these four categories.ResultsOf 389 participants, 134 (34.4%) were classified as PCOS and the remaining 255 (65.6%), as the non-PCOS population. Overall 45.2% of women had high BMI (≥ 23). Compared to non-PCOS subjects, women with PCOS had a higher BMI (mean (SD): 25.14 ± 6.46 vs 23.08 ± 4.36, p < 0.001). Women with PCOS and high BMI had increased hair growth with modified Ferriman-Gallwey (mFG) scores that were 2.96-fold higher versus healthy-normal BMI women (mean difference; 1.85, 95% CI 0.80–2.90). Compared to healthy-high BMI women, PCOS women with high BMI had significantly higher mean differences in mFG scores (1.79, 95% CI 0.64–2.93). In PCOS women, having high BMI also significantly increased mFG scores by 1.85-fold (mean difference; 1.82. 95% CI 0.52–3.12). This effect was mirrored by the additive effect of BMI and PCOS on free androgen index. No independent effect of high BMI on rates of oligomenorrhoea, antral follicle count, ovarian volume or serum androgens were observed.ConclusionsWe observed an additive effect of body weight to increase hair growth in women with PCOS. Maximum mFG scores were present in PCOS women with high BMI. Such increases in mFG score may affect the self-esteem of women with PCOS.