Introduction: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder that significantly affects adolescent girls, particularly those with overweight or obesity. However, data examining the determinants and metabolic profiles of PCOS among adolescents with overweight and obesity remain limited, especially in Malaysia. This protocol describes a case-control study investigating the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. Methodology: This study is designed as a case-control study involving adolescent girls aged 13–16 years with a body mass index z-score >+1 standard deviation. Cases are defined as adolescent girls with a confirmed diagnosis of PCOS based on the recommendations of the 2017 International Consortium of Paediatric Endocrinology (ICPE), while controls are those who do not meet the diagnostic criteria for PCOS. A total sample size of 440 participants is required. Participants will be recruited from 22 secondary schools selected from a list of schools in Kuala Lumpur. Data on sociodemographic characteristics, psychosocial health, physical activity, and dietary intake will be collected using structured questionnaires. Blood samples will be obtained and analyzed for diagnostic testing (free testosterone), exclusion tests (thyroid-stimulating hormone, folliclestimulating hormone, luteinizing hormone, estradiol, prolactin, and dehydroepiandrosterone sulfate), and biochemical parameters (liver function tests, lipid profile, hemoglobin A1c, fasting glucose, fasting insulin, and inflammatory markers). Results: The study is expected to generate comprehensive data on the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. The findings will inform early screening strategies and targeted interventions aimed at reducing long-term reproductive and cardiometabolic complications. Conclusion This protocol outlines a structured approach to investigating PCOS in adolescence and addresses current gaps in early identification and risk stratification among highrisk populations.
Adolescent ; Humans ; Case-Control Studies ; Overweight ; Polycystic Ovary Syndrome ; Obesity

Introduction: Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women of reproductive age. However, several endocrine disorders, particularly Cushing disease (CD), can closely mimic the clinical, biochemical, and radiological features of PCOS. This overlap may lead to misdiagnosis and delayed recognition of hypercortisolism, with significant metabolic and reproductive consequences. Case: We report a 24-year-old female with young-onset diabetes mellitus who was referred for endocrine co-management during admission for recurrent mons pubis and labial abscesses with poorly controlled glycemia. She had a 5-year history of progressive hirsutism, oligomenorrhoea, scalp hair loss, significant weight gain, and insulin resistance, and had previously been labelled as having PCOS during adolescence, with subsequent default of follow-up. On examination, she was obese (body mass index 33 kg/ m²) with plethoric facies, acanthosis nigricans, proximal myopathy, and hirsutism (Ferriman–Gallwey score 10), without overt virilization or acromegalic features. Biochemical evaluation demonstrated severe hyperandrogenism with markedly elevated total testosterone (7.05 nmol/L), suppressed gonadotropins, and adrenocorticotropic hormone (ACTH)-dependent hypercortisolism. Cortisol failed to suppress on low-dose dexamethasone testing, and 24-hour urinary free cortisol was markedly elevated (>4,900 nmol/24 h). Pelvic ultrasonography and computed tomography imaging showed polycystic ovarian morphology without evidence of an ovarian mass. Pituitary magnetic resonance imaging revealed a small right-sided pituitary microadenoma measuring 2.6 × 3.7 mm. Inferior petrosal sinus sampling demonstrated a central-to-peripheral ACTH gradient with adequate prolactin ratios, confirming pituitary CD. Conclusion This case highlights how Cushing disease can closely mimic PCOS, including polycystic ovarian morphology and hyperandrogenism. Progressive symptoms, severe biochemical androgen excess, and marked insulin resistance should prompt evaluation for secondary causes of hyperandrogenism, particularly hypercortisolism, to avoid delayed diagnosis and prolonged morbidity.
Female ; Hyperandrogenism ; Pituitary ACTH Hypersecretion ; Polycystic Ovary Syndrome

BACKGROUND

Polycystic ovarian syndrome (PCOS) is a common gynecologic endocrine disorder affecting between 2.2% and 26% of the population. It is typically characterized by hirsutism and signs of ovulatory dysfunction. Hirsutism is defined as the presence of excess body or facial terminal hair growth in females, following a male-like pattern. It is diagnosed using visual assessment methods, such as the modified Ferriman–Gallwey (mFG) scoring system, and biochemical tests, including measurements of total testosterone (tT) and the free androgen index (FAI).

The general objective of the study is to identify the correlation of visual scoring with the biochemical evaluation of hirsutism. Specific objectives include (1) to describe the visual and biochemical scores of hirsutism in PCOS patients and (2) to determine a cutoff score for the visual scoring of hirsutism among Filipinos.

This is a cross-sectional study done in a tertiary hospital. Ethical approval was obtained for this study. Patients who satisfied the inclusion criteria were included in the study. Age, height, weight, body mass index (BMI), and OB score were noted. Visual scoring for hirsutism using the mFG scoring system was performed. Blood extraction was done for testosterone and sex hormone-binding globulin tests. FAI was then computed and correlated with the mFG scores.

A total of 52 patients were identified. A positive correlation is noted between the mFG with testosterone and FAI. A positive correlation was also noted between the BMI with testosterone and FAI. An mFG value of >4 is an acceptable cutoff for Filipinos.

The study showed as the mFG score increases, FAI and tT levels also increase. It was also noted that as BMI increases, the FAI and tT levels are also expected to increase. It can also be concluded that a lower mFG cutoff value, >4, is applicable for Filipinos.

BACKGROUND AND OBJECTIVE

Polycystic ovarian syndrome (PCOS) is a complex disease associated with endometrial lesions. Local data on endometrial findings associated with PCOS are limited. This study aimed to determine the local prevalence and spectrum of endometrial findings and their association with clinical factors among Filipino women with PCOS.

This is a retrospective review of women aged 18–40 years old seen at a local tertiary hospital from January 2016 to December 2020 with ultrasound findings of polycystic ovaries based on Rotterdam criteria. The clinical data and ultrasound findings/impressions were reviewed. Histopathologic results when available were retrieved. Data were analyzed using descriptive statistics; abnormal endometrial findings were associated with clinical factors using binary logistic regression analysis.

A total of 177 women were included in the study, and 39 (22%) had abnormal endometrial findings by ultrasound including thickened endometrium (14.7%), polyp (5.1%), submucous myoma (1.1%), and malignancy (1.1%). Ultrasound findings that were significantly common with abnormal endometrium included thickening, nonuniform echogenicity, and the presence of vascularity. Irregular menses were more common in those with a normal endometrium, while heavy menses predominated in those with an abnormal endometrium, with statistically significant differences ( <0.001). The overall prevalence of obesity was 19.77%, but no clinical diseases were found significantly associated with abnormal endometrium. The prevalence of endometrial polyp and malignancy as confirmed by histopathology were 5.1% and 1.69%, respectively. No endometrial hyperplasia cases were reported.

Abnormal endometrial findings were relatively common among cases with polycystic ovaries, and most often, cases present with heavy menstrual bleeding. However, no predictable clinical factor can help identify PCOS patients with abnormal endometrial findings. Although malignancy was less common in the age group included in this study, the presence of abnormal sonographic findings would warrant further evaluation.

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

OBJECTIVE: To investigate the clinical therapeutic effect of Rendu Tongtiao acupuncture (acupuncture for regulating and improving the circulation of the conception and governor vessels) on hyperandrogenism (HA) in polycystic ovary syndrome (PCOS) with kidney-yin deficiency induced fire hyperactivity. METHODS: A total of 80 PCOS-HA patients were selected and randomly divided into an observation group and a control group, 40 cases in each group. In the control group, ethinylestradiol and cyproterone acetate tablets were administered orally,2 mg each time, once daily and for 21 consecutive days as one menstrual cycle. In the observation group, Rendu Tongtiao acupuncture was delivered at Qihai (CV6), Zhongwan (CV12), Guanyuan (CV4), Zhongji (CV3), Mingmen (GV4), Yaoyangguan (GV3), etc. once daily till ovulation, which was taken as the treatment session of one menstrual cycle. The treatment was completed after 3 menstrual cycles in each group. Before and after treatment, the serum levels of testosterone (T), dihydrotestosterone (DHT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), sex hormone-binding globulin (SHBG), and the scores of acne and hirsutism were compared in the two groups; besides, menstrual recovery rate, ovulation recovery rate, basic body temperature (BBT) biphasic rate and clinical effect were compared between the two groups. RESULTS: Compared with those before treatment, the levels of T, DHT, LH and PRL, as well as the scores of acne and hirsutism were reduced in the two groups after treatment (P<0.05), and the levels of FSH and SHBG were increased (P<0.05). After treatment, the levels of T, DHT, LH and PRL, as well as the scores of acne and hirsutism in the observation group were lower than those in the control group (P<0.05); and FSH and SHBG were higher (P<0.05). After treatment, the menstrual recovery rate and ovulation recovery rate, as well as BBT biphasic rate in the observation group increased in comparison with the control group (P<0.05). The total effective rate was 97.5% (39/40) in the observation group, which was higher than 82.4% (33/40) of the control group (P<0.05). CONCLUSION Rendu Tongtiao acupuncture can effectively regulate the secretion of hormones, alleviate the clinical symptoms of HA, and accelerate the recovery of menstruation and natural ovulation in patients with PCOS-HA of kidney-yin deficiency induced fire hyperactivity .
Humans ; Female ; Polycystic Ovary Syndrome/complications* ; Acupuncture Therapy ; Adult ; Young Adult ; Hyperandrogenism/blood* ; Yin Deficiency/therapy* ; Kidney/physiopathology* ; Acupuncture Points ; Testosterone/blood* ; Luteinizing Hormone/blood* ; Follicle Stimulating Hormone/blood* ; Adolescent

OBJECTIVE: To analyze the acupoint selection patterns and core prescriptions of acupuncture for polycystic ovary syndrome (PCOS) using data mining, and to explore the molecular mechanisms of core acupoints through network acupuncture medicine. METHODS: The randomized controlled trials (RCTs) on acupuncture for PCOS published from January 1, 2004 to July 21, 2024 were retrieved from CNKI, VIP, Wanfang, PubMed, and Web of Science databases. R software (version 4.4.0) was used for acupoint frequency and association rule analysis to identify core acupoint prescriptions. Potential targets were predicted via the STITCH and Swiss Target Prediction databases, and a "core prescription-active compounds-targets- PCOS" network was constructed. Cytoscape 3.7.1 was applied to build protein-protein interaction (PPI) networks of potential targets of core acupoint prescriptions. Key therapeutic targets were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses using the DAVID and Microbioinformatics platforms. RESULTS: A total of 176 RCTs were included, covering 208 prescriptions and 89 acupoints. The five most frequently used acupoints were Guanyuan (CV4), Sanyinjiao (SP6), Zigong (EX-CA1), Zusanli (ST36) and Zhongji (CV3). Association rule analysis yielded 13 core acupoint combinations, with Guanyuan (CV4), Sanyinjiao (SP6), Zigong (EX-CA1) and Zusanli (ST36) as the core prescription. Twenty-seven active compounds were involved, with 852 potential therapeutic targets, among which 208 targets overlapped with PCOS-related targets. Network acupuncture medicine analysis suggested that the core prescription may act through targets such as estrogen receptor 1 (ESR1), proto-oncogene tyrosine-protein kinase Src (SRC), signal transducer and activator of transcription 3 (STAT3), peroxisome proliferator-activated receptor gamma (PPARG), and RAC-alpha serine/threonine-protein kinase (AKT1). GO and KEGG analyses indicated that the main pathways included the hypoxia-inducible factor 1 (HIF-1) signaling pathway, phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, and advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, involving processes such as signal transduction, receptor complex formation, and cytokine activity. CONCLUSION The core acupoint prescription for PCOS might exert therapeutic effects through multiple targets and pathways, providing a theoretical basis for mechanistic research on acupoint prescriptions.
Humans ; Acupuncture Therapy ; Data Mining ; Acupuncture Points ; Polycystic Ovary Syndrome/metabolism* ; Female ; Protein Interaction Maps ; Randomized Controlled Trials as Topic

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

OBJECTIVE: To explore the effects of electroacupuncture (EA) on pregnancy outcomes after assisted reproduction and mitochondrial function of granulosa cells (GCs) in patients with polycystic ovary syndrome (PCOS) and phlegm-dampness syndrome. METHODS: In this randomized controlled trial, 90 infertile women with PCOS and phlegm-dampness syndrome were recruited between August 2022 and December 2022. Patients were randomly assigned to the EA and control groups using a random sequence of codes in the order of enrolment, with 45 in in each group. Both groups underwent the ovarian stimulation protocol. The patients in the EA group received EA therapy including Zhongwan (CV 12), Qihai (CV 6), bilateral Xuehai (SP 10), Sanyinjiao (SP 6), Yinlingquan (SP 9), Tianshu (ST 25), Zusanli (ST 36), and Fenglong (ST 40), and the patients in the control group was treated with pseudo-acupuncture. The intervention was 25 min twice a week for a total of 6 times until the trigger day after menstruation had ended in the cycle before oocyte retrieval. The primary outcomes were clinical pregnancy rate (CPR) and the number of high-quality embryos. The secondary outcomes were (1) pregnancy-related indicators, including fresh embryo transfer rate (ETR), ovarian hyperstimulation syndrome (OHSS) rate, early pregnancy loss rate (ePLR), ectopic pregnancy rate, live birth rate (LBR), and cumulative CPR; (2) mitochondrial autophagy and mitochondrial membrane potential (MMP) in GCs; and (3) scoring for Chinese medicine syndrome. Adverse events to assess clinical safety were also monitored. RESULTS: The cumulative CPR was significantly higher in the EA group (42/45, 93.3%) than in the control group (38/45, 84.4%, P=0.036). The number of high-quality embryos and fresh ETR in the EA group were higher than those in the control group (3.80±1.65 vs. 2.44±1.34, P<0.001; 46.7% vs 24.4%, P=0.028). Ectopic pregnancies were not observed in either group. There were no significant differences in the fresh CPR, OHSS rate, ePLR or LBR between the two groups (P>0.05). Compared with the control group, the EA group showed lower expression levels of miR-146a-5p mRNA and P62 protein in GCs and higher levels of MMP and the LC3-II/LC3-I protein ratio (all P<0.01). The phlegm-dampness syndrome scores of the EA group were significantly lower than those of the control group (P<0.01). CONCLUSIONS EA significantly improved pregnancy outcomes in patients with PCOS and phlegm dampness syndrome. Mechanistically, this effect may be related to EA in decreasing miR-146a-5p mRNA expression, promoting mitochondrial autophagy in GCs, and improving mitochondrial function, which may contribute to improved oocyte quality. (Trial registration No. ChiCTR2200062915).
Humans ; Female ; Polycystic Ovary Syndrome/therapy* ; Pregnancy ; Electroacupuncture ; Granulosa Cells/metabolism* ; Adult ; Mitochondria/metabolism* ; Pregnancy Outcome ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Infertility, Female/therapy*