Irregular Cycles, Ovulatory Disorders, and Cardiometabolic Conditions in a US-Based Digital Cohort.

Importance: Polycystic ovary syndrome (PCOS), characterized by irregular menstrual cycles and hyperandrogenism, is a common ovulatory disorder. Having an irregular cycle is a potential marker for cardiometabolic conditions, but data are limited on whether the associations differ by PCOS status or potential interventions. Objective: To evaluate the association of PCOS, time to regularity since menarche (adolescence), and irregular cycles (adulthood) with cardiometabolic conditions. Design, Setting, and Participants: This cross-sectional study used a large, US-based digital cohort of users of the Apple Research application on their iPhone. Eligibility criteria were having ever menstruated, living in the US, being at age of consent of at least 18 years (or 19 years in Alabama and Nebraska or 21 years in Puerto Rico), and being able to communicate in English. Participants were enrolled between November 14, 2019, and December 13, 2022, and completed relevant surveys. Exposures: Self-reported PCOS diagnosis, prolonged time to regularity (not spontaneously establishing regularity within 5 years of menarche), and irregular cycles. Main Outcomes and Measures: The primary outcome was self-reported cardiometabolic conditions, including obesity, prediabetes, type 1 and 2 diabetes, high cholesterol, hypertension, metabolic syndrome, arrhythmia, congestive heart failure, coronary artery disease, heart attack, heart valve disease, stroke, transient ischemic attack (TIA), deep vein thrombosis, and pulmonary embolism measured using descriptive statistics and logistic regression to estimate prevalence odds ratios (PORs) and 95% CIs. Effect modification by lifestyle factors was also estimated. Results: The study sample (N = 60 789) had a mean (SD) age of 34.5 (11.1) years, with 12.3% having PCOS and 26.3% having prolonged time to regularity. Among a subset of 25 399 participants who completed the hormonal symptoms survey, 25.6% reported irregular cycles. In covariate-adjusted logistic regression models, PCOS was associated with a higher prevalence of all metabolic and several cardiovascular conditions, eg, arrhythmia (POR, 1.37; 95% CI, 1.20-1.55), coronary artery disease (POR, 2.92; 95% CI, 1.95-4.29), heart attack (POR, 1.79; 95% CI, 1.23-2.54), and stroke (POR, 1.66; 95% CI, 1.21-2.24). Among participants without PCOS, prolonged time to regularity was associated with type 2 diabetes (POR, 1.24; 95% CI, 1.05-1.46), hypertension (POR, 1.09; 95% CI, 1.01-1.19), arrhythmia (POR, 1.20; 95% CI, 1.06-1.35), and TIA (POR, 1.33; 95% CI, 1.01-1.73), and having irregular cycles was associated with type 2 diabetes (POR, 1.36; 95% CI, 1.08-1.69), high cholesterol (POR, 1.17; 95% CI, 1.05-1.30), arrhythmia (POR, 1.21; 95% CI, 1.02-1.43), and TIA (POR, 1.56; 95% CI, 1.06-2.26). Some of these associations were modified by high vs low body mass index or low vs high physical activity. Conclusions and Relevance: These findings suggest that PCOS and irregular cycles may be independent markers for cardiometabolic conditions. Early screening and intervention among individuals with irregular menstrual cycles may be beneficial.

Effect of polycystic ovary syndrome on the life quality of young women.

OBJECTIVE: The study evaluated the opinions of polycystic ovary syndrome on the life quality of women. METHODS: A total of 249 women with polycystic ovary syndrome participated in this descriptive study between October 2022 and July 2023 in Istanbul, Turkey. FINDINGS: Polycystic Ovary Syndrome and Quality of Life was significantly correlated with age (p=0.000) and frequent weight loss diets (p=0.000) (p<0.01). Among the Polycystic Ovary Syndrome and Quality of Life total score and polycystic ovary syndrome symptoms, those with hormone imbalance and insulin resistance had the highest mean scores, while those with menstrual irregularity and fatigue had the lowest. CONCLUSION: Advancing age changes the quality of life of women with polycystic ovary syndrome. To prevent the negative impact of polycystic ovary syndrome on women's quality of life, it is recommended that health professionals develop effective care plans utilizing available evidence.

Is the MIND diet useful for polycystic ovary syndrome? A case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent cause of ovulatory infertility and endocrine abnormalities in reproductive-age women. Although the MIND diet has been introduced to improve brain function, evidence shows that the MIND diet is rich in beneficial food groups that can have a preventive effect on other metabolic disorders. The present study was conducted to investigate the association between adherence to the MIND diet and PCOS. METHODS: This age and BMI frequency-matched case-control study was conducted on 216 women between January 2018 and March 2019 in Yazd, Iran. PCOS was diagnosed based on Rotterdam criteria. Participants were selected by convenience sampling method. The validated 178-item food frequency questionnaire was used to assess the usual dietary intake. Logistic regression was used to estimate the association between the MIND diet and PCOS. RESULTS: The findings of the present study showed a significant inverse association between adherence to the MIND diet and PCOS in the crude model (OR for T3 vs. T1: 0.12 (95% CI: 0.05-0.25), P-value < 0.001) and multivariable-adjusted model including energy intake, age, BMI, waist circumference, marital status, pregnancy history, drug use history, education and physical activity (OR for T3 vs. T1 = 0.08 (95% CI: 0.03-0.19), P-value < 0.001). Adherence to the MIND diet had a protective effect of 92%. CONCLUSION: Although the results of the present study showed that higher adherence to the MIND diet is associated with a lower risk of PCOS, more studies are needed to confirm these findings in the future.

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

OBJECTIVE: This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. METHODS: This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). RESULT: In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. CONCLUSION: The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

The effect of social network based motivational interviewing on health behaviors among infertile women with polycystic ovary syndrome: A randomized controlled trial.

Polycystic ovary syndrome is one of the commonest and complex endocrine disorders in females of reproductive age. Attention to self-care behaviors such as health-promoting behaviors can improve physiological and psychological conditions in women with PCOS. This study aimed to determine the efficacy of Social Network-Based Motivational Interviewing on health-promoting behaviors and quality of life of infertile women with polycystic ovary syndrome. In this randomized controlled trial, 60 infertile women with polycystic ovary syndrome were randomly selected and assigned to the interventio (n = 30) or a control group (n = 30). Participants in the control group received routine care. Those in the intervention group received five motivational group sessions in WhatsApp, which were conducted in five groups of six participants each. The data related to health-promoting behaviors and quality of life were collected through an online questionnaire. Both groups were followed up immediately and 2 months after the intervention. Data collected in the two stages were analyzed using the paired-samples t-test, Chi-square, and repeated measures analysis. No significant difference was observed between the two groups before the intervention means health-promoting behaviors and quality of life scores (p>0.05). Immediately and two months after the intervention, the mean scores of health-promoting behaviors and their domains increased in the intervention group. This increase is statistically compared to the first test, and the scores obtained by the control group in the second (p< 0.001, ES = 1.5) and the third test (p< 0.001, ES= 1.3) were significant. The score of the quality of life variable increase was not statistically significant compared to the first test and also to the scores obtained by the control group. However According to the Generalized estimating equations (GEE) test, the changes in quality of life score between the two groups in the three stages of measurement are statistically significant. WhatsApp support increases the health-promoting self-care behaviors rate and has favorable effects on follow-up.Trial registration: Iranian Registry for Clinical Trial (the link to trial: https://www.irct.ir/trial/48089 ). Registered August 11 2020.

[Bushen Culuan Formula in treatment of infertility caused by polycystic ovary syndrome].

This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.

Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis.

OBJECTIVE: To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS: Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS: The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.

Alexithymia and Quality of Life in Saudi Women with Polycystic Ovary Syndrome: A Community-Based Study.

BACKGROUND The endocrine metabolic disorder polycystic ovary syndrome (PCOS) is quite common among women. Women with PCOS show a compromised health-related quality of life (HRQoL), impaired emotional well-being, and alexithymia, a neuropsychological phenomenon conceptualized as difficulty in recognizing and expressing one's emotions. However, the relationship between alexithymia and HRQoL in women with PCOS is unclear. This study aimed to investigate the impact of alexithymia on HRQoL in women with PCOS in Saudi Arabia. MATERIAL AND METHODS This descriptive cross-sectional, community-based study enrolled 518 female patients with a diagnosis of PCOS from all age groups. The patients were surveyed via a self-administered questionnaire from December 2022 to January 2023. The survey encompassed sociodemographic data, the 20-item Toronto Alexithymia Scale (TAS-20), and HRQoL 15-dimensional scale (15D). RESULTS This study included 320 participants (61.8%) with alexithymia. A significant association was found between alexithymia and low HRQoL 15D scores in patients with PCOS. Specifically, scores on the TAS-20 subscales related to difficulty in identifying feelings and describing feelings were positively correlated with HRQoL (P=0.000). However, externally oriented thinking subscale scores were not positively correlated with HRQoL (P=0.44). CONCLUSIONS The presence of alexithymia is associated with poor HRQoL in women with PCOS, which is more pronounced among those who received a diagnosis ≥4 years ago. Alexithymia must be considered when assessing the HRQoL of patients with PCOS, considering the relatively high prevalence of alexithymia in these patients.

Polycystic ovary syndrome.

Despite affecting ~11-13% of women globally, polycystic ovary syndrome (PCOS) is a substantially understudied condition. PCOS, possibly extending to men's health, imposes a considerable health and economic burden worldwide. Diagnosis in adults follows the International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome, requiring two out of three criteria - clinical or biochemical hyperandrogenism, ovulatory dysfunction, and/or specific ovarian morphological characteristics or elevated anti-Müllerian hormone. However, diagnosing adolescents omits ovarian morphology and anti-Müllerian hormone considerations. PCOS, marked by insulin resistance and hyperandrogenism, strongly contributes to early-onset type 2 diabetes, with increased odds for cardiovascular diseases. Reproduction-related implications include irregular menstrual cycles, anovulatory infertility, heightened risks of pregnancy complications and endometrial cancer. Beyond physiological manifestations, PCOS is associated with anxiety, depression, eating disorders, psychosexual dysfunction and negative body image, collectively contributing to diminished health-related quality of life in patients. Despite its high prevalence persisting into menopause, diagnosing PCOS often involves extended timelines and multiple health-care visits. Treatment remains ad hoc owing to limited understanding of underlying mechanisms, highlighting the need for research delineating the aetiology and pathophysiology of the syndrome. Identifying factors contributing to PCOS will pave the way for personalized medicine approaches. Additionally, exploring novel biomarkers, refining diagnostic criteria and advancing treatment modalities will be crucial in enhancing the precision and efficacy of interventions that will positively impact the lives of patients.

Comorbidities in women with polycystic ovary syndrome: a sibling study.

BACKGROUND: Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. PCOS may be influenced by prenatal androgen excess, poor intrauterine or childhood environmental factors, childhood obesity and learned health risk behaviors. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. METHODS: This total-population register-based cohort study included 333,999 full sisters, born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjects´ early-life and social characteristics. In the main analysis, sister fixed effects (FE) models were used to control for all time-invariant factors that are shared among sisters, thereby testing whether the association between PCOS and examined comorbidities is influenced by unobserved familial environmental, social or genetic factors. RESULTS: Three thousand five hundred seventy women in the Sister sample were diagnosed with PCOS, of whom 14% had obesity, 8% had depression, 7% had anxiety and 4% experienced sleeping, sexual and eating disorders (SSE). Having PCOS increased the odds of obesity nearly 6-fold (adjusted OR (aOR): 5.9 [95% CI:5.4-6.5]). This association was attenuated in models accounting for unobserved characteristics shared between full sisters, but remained considerable in size (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). For depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when controlling for factors shared between sisters. Being diagnosed with SSE disorders yielded a 2.4 aOR (95% CI:2.0-2.6) when controlling for a comprehensive set of individual-level confounders, which only decreased slightly when controlling for factors at the family level such as shared genes or parenting style. Accounting for differences between sisters in observed early-life circumstances influenced the estimated associations marginally. CONCLUSION: Having been diagnosed with PCOS is associated with a markedly increased risk of obesity and sleeping, sexual and eating disorders, also after accounting for factors shared between sisters and early-life conditions.

Nutritional management recommendation systems in polycystic ovary syndrome: a systematic review.

BACKGROUND: People with polycystic ovary syndrome suffer from many symptoms and are at risk of developing diseases such as hypertension and diabetes in the future. Therefore, the importance of self-care doubles. It is mainly to modify the lifestyle, especially following the principles of healthy eating. The purpose of this study is to review artificial intelligence-based systems for providing management recommendations, especially food recommendations. MATERIALS AND METHODS: This study started by searching three databases: PubMed, Scopus, and Web of Science, from inception until 6 June 2023. The result was the retrieval of 15,064 articles. First, we removed duplicate studies. After the title and abstract screening, 119 articles remained. Finally, after reviewing the full text of the articles and considering the inclusion and exclusion criteria, 20 studies were selected for the study. To assess the quality of articles, we used criteria proposed by Malhotra, Wen, and Kitchenham. Out of the total number of included studies, seventeen studies were high quality, while three studies were moderate quality. RESULTS: Most studies were conducted in India in 2021. Out of all the studies, diagnostic recommendation systems were the most frequently researched, accounting for 86% of the total. Precision, sensitivity, specificity, and accuracy were more common than other performance metrics. The most significant challenge or limitation encountered in these studies was the small sample size. CONCLUSION: Recommender systems based on artificial intelligence can help in fields such as prediction, diagnosis, and management of polycystic ovary syndrome. Therefore, since there are no nutritional recommendation systems for these patients in Iran, this study can serve as a starting point for such research.

Is polycystic ovary syndrome a risk factor for depression and anxiety?: a cross-sectional study.

OBJECTIVE: The objective of this study was to learn more about the prevalence and pathophysiology of depression and anxiety that may be caused by polycystic ovary syndrome and to make plans for taking necessary precautions for this vulnerable group. METHODS: This case-control study was conducted between January 2022 and October 2022. A total of 120 women with polycystic ovary syndrome and 143 controls were included in the study. All healthy volunteers and women with polycystic ovary syndrome were evaluated using self-administered questionnaires and physical examination. Anthropometric data such as weight and height and laboratory value were documented. RESULTS: There was no significant difference between the groups in terms of demographic characteristics. When the Hospital Anxiety and Depression Scale scores of both groups were compared, both depression and anxiety scores were found to be significantly higher in women with polycystic ovary syndrome compared with the control group (OR: 3.319, 95%CI, 1.563-7.047, p<0.001 and OR: 3.238, 95%CI, 1.659-6.315, p<0.001). In the Hospital Anxiety and Depression Scale questionnaire, the rate of irregular menstruation and Ferriman-Gallwey score were statistically significant in women with polycystic ovary syndrome with high depression and anxiety scores. While serum LH levels and LH/FSH ratios were significantly different in women with polycystic ovary syndrome with high depression scores, serum LH, LH:FSH ratios, and serum total testosterone levels were found significant in women with polycystic ovary syndrome with high anxiety scores. CONCLUSION: It is clear that depression and anxiety are more common in patients with polycystic ovary syndrome than in healthy women. Our findings support previous recommendations regarding routine screening for depression and anxiety in this population.

Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.

OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Effect of vitamin D in addition to letrozole on the ovulation rate of women with polycystic ovary syndrome: protocol of a multicentre randomised double-blind controlled trial.

INTRODUCTION: Low vitamin D status is prevalent among women with polycystic ovary syndrome (PCOS). The objective of the study is to assess the effect of vitamin D supplementation on (1) the ovulation rate to letrozole and (2) other reproductive, endocrine and metabolic outcomes after 1 year of supplementation in women with PCOS. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blind, controlled clinical trial. A total of 220 anovulatory women with PCOS diagnosed by the Rotterdam criteria will be recruited. They will be randomly assigned to either the (1) vitamin D supplementation group or (2) placebo group. Those in the vitamin D group will take oral Vitamin D3 50 000 IU/week for 4 weeks, followed by 50 000 IU once every 2 weeks for 52 weeks. Those who remain anovulatory after 6 months will be treated with a 6-month course of letrozole (2.5 mg to 7.5 mg for 5 days per cycle titrated according to response) for ovulation induction. The primary outcome is the ovulation rate. All statistical analyses will be performed using intention-to-treat and per protocol analyses. ETHICS AND DISSEMINATION: Ethics approval was sought from the Institutional Review Board of the participating units. All participants will provide written informed consent before joining the study. The results of the study will be submitted to scientific conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04650880.

Hyperlipidemia Prevention and Management Utilizing Lifestyle Changes.

Hyperlipidemia incidence is on the rise and lifestyle behavior change is the first-line therapy. Left untreated, hyperlipidemia can result in cardiovascular disease leading to increased morbidity and mortality in persons worldwide. Evidence has demonstrated behavioral changes such as increased exercise, healthy nutrition, smoking cessation, alcohol abstinence, and other lifestyle modification interventions significantly decrease the incidence and severity of hyperlipidemia. The purpose of this article is to review the evidence of lifestyle interventions in preventing and managing hyperlipidemia and to suggest innovative ways to integrate those techniques into clinical practice. Recommendations on hyperlipidemia specific to pregnancy, polycystic ovary syndrome, and estrogen deficiency are also discussed.