of mechanisms linking obesity with PCOS. PCOS indicates polycystic...

Clinical Value and Mechanism Exploration of Serum miR-379 in Obesity-Polycystic Ovary Syndrome

Article

Full-text available

Jun 2024

Objective As a common endocrine and metabolic disorder, polycystic ovary syndrome (PCOS) is mostly associated with an obese phenotype. The present research focuses on the clinical significance of miR-379 in obesity-PCOS and attempts to elucidate its potential mechanisms. Methods Healthy individuals (n = 46), obesity-PCOS (n = 92), and non-obesity PCOS (n = 31) subjects were enrolled. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the level of serum miR-379. The receiver operating characteristic (ROC) curve and logistic regressions were applied to reveal the diagnostic significance. Dual luciferase reporters were performed to validate the targeting relationships. And cell count kit (CCK-8) assay was used to detect cell proliferation. Results Serum miR-379 was highly expressed in PCOS patients (P < 0.05), in especially obesity-PCOS patients. Higher miR-379 was associated with greater body mass index (BMI), higher bioavailable testosterone (bT), and greater insulin resistance (IR). Additionally, miR-379 was an independent risk factor for the development of obesity-PCOS. The sensitivity of miR-379 in identifying patients with obesity-PCOS from healthy or non-obesity-PCSO patients was 81.52% and 72.83%, and the specificity was 86.96% and 80.65%. Semaphorin 3 A (SEMA3A) was identified as a target of miR-379 and was reduced in the patients with obesity PCOS (P < 0.05). Inhibition of miR-375 reduced KGN proliferation, but this reduction was partially restored by silencing of SEMA3A (P < 0.05). Conclusion Elevated miR-379 assists the diagnosis of obesity-PCOS and regulates the proliferation of KGN by targeting SEMA3A engaged in disease development.

The Assessment of Women's Health-Related Quality of Life and Knowledge Gaps on Poly-Cystic Ovarian Syndrome (PCOS) has Implications for Better Self-Care and Educational Programs

Article

Jun 2024

This is an Open Access Journal / article distributed under the terms of the Creative Commons Attribution License (CC BY-NC-ND 3.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. All rights reserved. Women have a variety of health conditions that may result in a range of health-related issues. One of the main causes of delayed identification or inadequate disease self-management in such circumstances is ignorance. Furthermore, one of the biggest barriers to treating such conditions may be the ease or freedom with which one can speak or get knowledge. PCOS is a syndrome that affects women who are of reproductive years and has the potential to result in infertility. Patients may experience anxiety as a result of the condition developing at such a young age, overall PCOS has serious side effects that can negatively impact a person's lifestyle and general health. Consequently, it is imperative that women become more knowledgeable about the illness and how to manage it on their own. The aim of the investigation is to determine the degree of knowledge regarding PCOS and the differences in health-related quality of life (HRQoL) between the women in the group used as a control and those in the treatment group, who are between the generations of 18 and 49.The research was quantifiable along with comparable by design. The PCOS knowledge and Health Management Questionnaire was used in the study. Having 140 res-ponders in the sample who had gone through participation assessment. Both psycho-social and physiological impacts diverged significantly comparing both of the groups. Perhaps as a result of their own experiences, patients who have been diagnosed as having PCOS typically understand this disorder well. In all categories, there is still a lack of knowledge regarding risk factors, signs, age categories most impacted by PCOS, hormonal changes, and hirsutism. Regarding PCOS, about ABSTRACT RESEARCH ARTICLE RESEARCH ARTICLE Indian Journal of Natural Sciences www.tnsroindia.org.in ©IJONS Vol.15 / Issue 83 / Apr / 2024 International Bimonthly (Print)-Open Access ISSN: 0976-0997 2 half of the respondents had inadequate understanding and habits associated with health. Women who have been tested or suspect PCOS need to consult a doctor right away because getting medical care for PCOS shortly after diagnosis may enhance their standard of living. The creation and promotion of efficient strategies for raising education within women through the use of interaction and technological advances on the internet is necessary.

DECIPHERING THE INTRICATE NETWORK OF POLY CYSTIC OVARIAN SYNDROME: A THOROUGH EXAMINATION OF HORMONAL AND DEMOGRAPHIC INFLUENCES

Article

Jun 2024

One of the most prevalent hormonal disorders affecting women who are of reproductive age is PCOS, a serious public health concern. Insulin resistance is significantly more common together with hirsutism, polycystic ovaries, and oligo/anovulatory periods as typical symptoms and other multitude of chronic health issues that impact quality of life are linked to PCOS.PCOS patient and control group (non-PCOS) hormonal profiles are compared in this study.TSH, FSH, LH, and AMH are measured in this research. The results clarify the hormonal irregularities and consequences of PCOS.The data shows that women with PCOS had significantly greater AMH than controls, with a sensitivity and specificity of 93%.AMH has an NPV and PPV of 83% and 97%, respectively.The majority of PCOS patients reported higher LH levels than the control group, which had 86% sensitivity and 88% specificity. The LH level is impacted by PCOS, as seen by the 95% of PPV and 69%, of NPV.The FSH levels of controls and PCOS patients are comparable. Since FSH levels are comparable, the primary hormonal imbalance in PCOS is probably elevated LH and AMH. PCOS patients showed higher TSH levels than the control group, which may cause thyroid issues since 43% of PCOS patients had elevated TSH.These findings illuminate PCOS hormone abnormalities. Furthermore, people with PCOS are more prone than the general population to suffering from the morbidity related to metabolic and cardiovascular diseases.Understanding the hormonal imbalances linked to PCOS makes future research easier, which is required to understand the etiology of PCOS and hormone-regulated PCOS treatment.

The signaling pathways in obesity‐related complications

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Full-text available

Jun 2024

Obesity, a rapidly expanding epidemic worldwide, is known to exacerbate many medical conditions, making it a significant factor in multiple diseases and their associated complications. This threatening epidemic is linked to various harmful conditions such as type 2 diabetes mellitus, hypertension, metabolic dysfunction‐associated steatotic liver disease, polycystic ovary syndrome, cardiovascular diseases (CVDs), dyslipidemia, and cancer. The rise in urbanization and sedentary lifestyles creates an environment that fosters obesity, leading to both psychosocial and medical complications. To identify individuals at risk and ensure timely treatment, it is crucial to have a better understanding of the pathophysiology of obesity and its comorbidities. This comprehensive review highlights the relationship between obesity and obesity‐associated complications, including type 2 diabetes, hypertension, (CVDs), dyslipidemia, polycystic ovary syndrome, metabolic dysfunction‐associated steatotic liver disease, gastrointestinal complications, and obstructive sleep apnea. It also explores the potential mechanisms underlying these associations. A thorough analysis of the interplay between obesity and its associated complications is vital in developing effective therapeutic strategies to combat the exponential increase in global obesity rates and mitigate the deadly consequences of this polygenic condition.

Genes linked to obesity-related infertility: bridging the knowledge gap

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Full-text available

Jun 2024

Jason Zhu

Genetic factors play a pivotal role in the complex relationship between obesity and infertility. This article delves into the genetics of obesity-related infertility, focusing on the essential genes and mechanisms in both sexes. We explored infertility factors in obese females, focusing on polycystic ovary syndrome (PCOS) and the influence of genes like insulin receptor (INSR), androgen receptor (AR), and follicle-stimulating hormone receptor (FSHR). Epigenetic changes are believed to contribute to PCOS-related infertility. The impact of adipokines and inflammation on obesity-related infertility has been discussed, with genes such as fat mass and obesity (FTO) and melanocortin-4-receptor (MC4R) playing significant roles. Genetic factors affecting sperm quality and function, including nuclear receptor subfamily 3 group C member 1 (NR3C1) and methylenetetrahydrofolate reductase (MTHFR), have been investigated in obesity-related infertility in males. Hormonal dysregulation influenced by genetic markers, such as leptin receptor (LEPR), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), was also examined. Genetic factors play a vital role in obesity-related infertility in both sexes. Genes involved in metabolism, hormonal regulation, and inflammation contribute to the complex association between obesity and infertility. Epigenetic changes further complicate the relationship. Understanding these genetic mechanisms is essential to address obesity-related infertility and develop personalized interventions.

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

Article

Full-text available

May 2024
GYNECOL ENDOCRINOL

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.

Nutritional Considerations During Major Weight Loss Therapy: Focus on Optimal Protein and a Low-Carbohydrate Dietary Pattern

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May 2024

Purpose of Review Considering the high prevalence of obesity and related metabolic impairments in the population, the unique role nutrition has in weight loss, reversing metabolic disorders, and maintaining health cannot be overstated. Normal weight and well-being are compatible with varying dietary patterns, but for the last half century there has been a strong emphasis on low-fat, low-saturated fat, high-carbohydrate based approaches. Whereas low-fat dietary patterns can be effective for a subset of individuals, we now have a population where the vast majority of adults have excess adiposity and some degree of metabolic impairment. We are also entering a new era with greater access to bariatric surgery and approval of anti-obesity medications (glucagon-like peptide-1 analogues) that produce substantial weight loss for many people, but there are concerns about disproportionate loss of lean mass and nutritional deficiencies. Recent Findings No matter the approach used to achieve major weight loss, careful attention to nutritional considerations is necessary. Here, we examine the recent findings regarding the importance of adequate protein to maintain lean mass, the rationale and evidence supporting low-carbohydrate and ketogenic dietary patterns, and the potential benefits of including exercise training in the context of major weight loss. Summary While losing and sustaining weight loss has proven challenging, we are optimistic that application of emerging nutrition science, particularly personalized well-formulated low-carbohydrate dietary patterns that contain adequate protein (1.2 to 2.0 g per kilogram reference weight) and achieve the beneficial metabolic state of euketonemia (circulating ketones 0.5 to 5 mM), is a promising path for many individuals with excess adiposity. Graphical Abstract Created with Biorender.com.

Associations between Polycystic Ovary Syndrome (PCOS) and Antibiotic Use: Results from the UAEHFS

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Full-text available

Apr 2024

Women with polycystic ovary syndrome (PCOS) have a higher susceptibility to infections compared to those without PCOS. Studies evaluating antibiotic use based on PCOS status are scarce. Therefore, we aimed to (i) assess the associations between self-reported PCOS and antibiotic use, and (ii) whether PCOS treatment and the age at PCOS diagnosis modified the associations above. This cross-sectional analysis used the United Arab Emirates Healthy Future Study (UAEHFS) conducted from February 2016 to March 2023 involving 2063 Emirati women aged 18–62 years. We performed ordinal logistic regressions under unadjusted and demographic-health-characteristic-adjusted models to obtain the odds ratios (ORs) and 95% confidence intervals (CIs) to analyze PCOS and antibiotic use. Subgroup analyses were performed by treatment status and age at diagnosis. We found that women with PCOS were 55% more likely to frequently take a course of antibiotics in the past year (aOR 1.55; 95% CI 1.26–1.90). Similar likelihoods were also found among those being treated for PCOS and those without treatment but with a PCOS diagnosis at ≤25 years. Our study suggests that PCOS was associated with an increased use of antibiotics among Emirati women. Understanding the frequent antibiotic use susceptibility among those with PCOS may improve antibiotic use surveillance and promote antibiotic stewardship in these at-risk individuals.

Comparative efficacy of exercise, diet and/or pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity: a systematic review and network meta-analysis

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Full-text available

Apr 2024
HUM REPROD UPDATE

BACKGROUND The increasing prevalence of obesity worldwide poses a significant threat to reproductive function owing, in part, to hormonal disturbances caused by negative feedback between excess adiposity and the hypothalamic–pituitary–ovarian axis. Consequently, finding the most appropriate strategies to lose weight and improve ovulation in women with overweight or obesity is a clinically relevant matter that needs to be investigated. A comprehensive comparison of the independent and combined efficacy of lifestyle and/or pharmacological interventions on BMI, ovulation, and hormonal profile in women with overweight or obesity at risk of anovulatory infertility would facilitate improving fertility strategies in this population. OBJECTIVE AND RATIONALE This study aimed to evaluate the comparative efficacy of exercise, diet, and pharmacological interventions on BMI, ovulation, and hormonal profile in reproductive-aged women with overweight or obesity. SEARCH METHODS A systematic review was performed by searching PubMed, Scopus, Web of Science, PsycINFO, and Cochrane Library up to 14 December 2023, for randomized controlled trials assessing the effects of exercise, diet and/or pharmacological interventions (i.e. weight-lowering drugs or ovulation inducers) on BMI, ovulation, and/or hormonal profile in reproductive-aged women with overweight or obesity. We performed frequentist random-effect network meta-analyses and rated the certainty of the evidence. The primary outcomes were BMI and ovulation rate, and the secondary outcomes were serum reproductive hormone levels (gonadotrophins, androgens, or oestrogens). We performed sensitivity analyses, including the studies that only involved women with PCOS. OUTCOMES Among 1190 records screened, 148 full texts were assessed for eligibility resulting in 95 trials (9910 women), of which 53% presented a high or unclear risk of bias. The network meta-analyses revealed that, compared to control: diet combined with weight-lowering drugs (mean difference (MD) −2.61 kg/m2; 95% CI −3.04 to −2.19; τ2 = 0.22) and adding exercise (MD −2.35 kg/m2; 95% CI −2.81 to −1.89; τ2 = 0.22) led to the greatest decrease in BMI; exercise combined with diet and ovulation inducers (risk ratio (RR) 7.15; 95% CI 1.94–26.40; τ2 = 0.07) and exercise combined with diet and weight-lowering drugs (RR 4.80; 95% CI 1.67–13.84; τ2 = 0.07) produced the highest increase in ovulation rate; and exercise combined with diet and weight-lowering drugs was the most effective strategy in reducing testosterone levels (standardized mean difference (SMD) −2.91; 95% CI −4.07 to −1.74; τ2 = 2.25), the third most effective strategy in increasing sex hormone-binding globulin levels (SMD 2.37; 95% CI 0.99–3.76; τ2 = 2.48), and it was coupled with being ranked first in terms of free androgen index reduction (SMD −1.59; 95% CI −3.18 to 0.01; τ2 = 1.91). The surface under the cumulative ranking curve scores suggested that: diet combined with weight-lowering drugs is the strategy most likely (94%) to produce the highest BMI reduction; and exercise combined with diet and ovulation inducers is the strategy most likely (89%) to produce the highest ovulation rate improvement. The sensitivity analyses, which exclusively included studies involving women diagnosed with PCOS, were consistent with the results presented above. WIDER IMPLICATIONS Overall, the findings of this network meta-analysis indicate that the combination of exercise, diet, and pharmacological interventions is effective for weight loss, improving ovulation, and normalizing the androgen levels of women with overweight or obesity. Although higher quality studies are needed, these results support that the optimal treatment strategy for women with overweight or obesity wishing to conceive must consider exercise, diet, and pharmacological interventions during the shared decision-making process.

Mechanism of elevated LH/FSH ratio in lean PCOS revisited: a path analysis

Article

Full-text available

Apr 2024

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5–20% of reproductive-age women. However, the treatment of PCOS is mainly based on symptoms and not on its pathophysiology. Neuroendocrine disturbance, as shown by an elevated LH/FSH ratio in PCOS patients, was thought to be the central mechanism of the syndrome, especially in lean PCOS. LH and FSH secretion are influenced by GnRH pulsatility of GnRH neurons in the hypothalamus. Kisspeptin is the main regulator of GnRH secretion, whereas neurokinin B (NKB) and dynorphin regulate kisspeptin secretion in KNDy neurons. This study aims to deepen the understanding of the neuroendocrine disorder in lean PCOS patients and its potential pathophysiology-based therapy. A cross-sectional study was performed at Dr. Cipto Mangunkusumo Kencana Hospital and the IMERI UI HRIFP cluster with 110 lean PCOS patients as subjects. LH, FSH, LH/FSH ratio, kisspeptin, NKB, dynorphin, leptin, adiponectin, AMH, fasting blood glucose, fasting insulin, HOMA-IR, testosterone, and SHBG were measured. Bivariate and path analyses were performed to determine the relationship between variables. There was a negative association between dynorphin and kisspeptin, while NKB levels were not associated with kisspeptin. There was no direct association between kisspeptin and the LH/FSH ratio; interestingly, dynorphin was positively associated with the LH/FSH ratio in both bivariate and pathway analyses. AMH was positively correlated with the LH/FSH ratio in both analyses. Path analysis showed an association between dynorphin and kisspeptin levels in lean PCOS, while NKB was not correlated with kisspeptin. Furthermore, there was a correlation between AMH and the LH/FSH ratio, but kisspeptin levels did not show a direct significant relationship with the LH/FSH ratio. HOMA-IR was negatively associated with adiponectin levels and positively associated with leptin and FAI levels. In conclusion, AMH positively correlates with FAI levels and is directly associated with the LH/FSH ratio, showing its important role in neuroendocrinology in lean PCOS. From the path analysis, AMH was also an intermediary variable between HOMA-IR and FAI with the LH/FSH ratio. Interestingly, this study found a direct positive correlation between dynorphin and the LH/FSH ratio, while no association between kisspeptin and the LH/FSH ratio was found. Further research is needed to investigate AMH and dynorphin as potential therapeutic targets in the management of lean PCOS patients.

of mechanisms linking obesity with PCOS. PCOS indicates polycystic ovary syndrome.

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