Association of severity of menstrual dysfunction with cardiometabolic risk markers among women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. MATERIAL AND METHODS: This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. RESULTS: A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. CONCLUSIONS: PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. METHODS: In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). FINDINGS: Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5-10·0) in the surgical group and 2 (0·0-4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5-4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. INTERPRETATION: Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. FUNDING: The Jon Moulton Charity Trust.

Prevalence of endocrine disorders in 304 premenopausal women referred with oligomenorrhoea.

INTRODUCTION: We aimed to evaluate 304 premenopausal women admitted to our clinic for oligomenorrhoea, and to screen for Cushing's syndrome (CS) in this population. MATERIAL AND METHODS: The study included 304 premenopausal women referred to our clinic for oligomenorrhoea. Anthropometric measurements and Ferriman-Gallwey score were evaluated, and thyroid hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, prolactin, dehydroepiandrosterone sulphate (DHEA-S), and 17-hydroxyprogesterone (17-OHP) levels were measured in all patients. If basal 17-OHP was > 2 ng/mL, we evaluated adrenocorticotropic hormone (ACTH)-stimulated 17-OHP levels. CS was screened by 1 mg-dexamethasone suppression test, and if the cortisol value was > 1.8 µg/dL, we performed additional confirmatory tests, and if necessary, pituitary magnetic resonance imaging (MRI) and inferior petrosal sinus sampling (IPSS) were performed. RESULTS: The most common cause of oligomenorrhoea was polycystic ovary syndrome (PCOS) that was detected in 81.57% of cases, followed by hyperprolactinemia at 7.23% and hypothalamic anovulation at 5.26%. The prevalence of premature ovarian failure (POF) was 1.6%, and non-classical congenital adrenal hyperplasia (NCAH) was 1.97%. CS was detected in 7 (2.30%) patients. All the patients with CS were found to have Cushing's disease (CD). Although 3 patients with CD had classical signs and symptoms, 4 had none. Patients with CD had similar total testosterone values to those in the PCOS and NCAH groups, but they had significantly higher DHEA-S compared to both groups (CD vs. PCOS, p = 0.001 and CD vs. NCAH, p = 0.030). CONCLUSIONS: We found higher prevalence of CS in patients with oligomenorrhoea even in the absence of clinical signs. Therefore, we suggest routine screening for CS during the evaluation of patients with oligomenorrhoea and/or PCOS. The likelihood of CS is greater in patients with high androgen, especially DHEA-S levels.

The impact of sleeve gastrectomy on polycystic ovarian syndrome: a single-center 1-year cohort study.

BACKGROUND AND AIM: Obesity is one of the risk factors for polycystic ovarian syndrome (PCOS), and weight loss is the mainstay of treatment. This study investigates the effects of sleeve gastrectomy on clinical and paraclinical signs and symptoms of PCOS patients referred to a tertiary hospital. METHODS: Female patients with a definite diagnosis of PCOS and body mass index (BMI) > 40 kg/m2 who were candidates for sleeve gastrectomy were enrolled in this cohort study and followed for 1 year postoperatively. Clinical signs and symptoms of PCOS, sonographic examination, and laboratory hormonal assessments were assessed preoperatively and 1 year following surgery. RESULTS: Fifty patients enrolled in the study. The mean age of patients was 31.69 ± 9.54 years. The mean BMI before and after the surgery was 44.28 ± 3.03 and 29.37 ± 2.41 kg/m2, respectively. Oligomenorrhea was improved in 66% of patients. According to the sonographic criteria, PCOS was improved in 74% of patients. After a year post-operation, while the mean serum levels of the follicular stimulating hormone (FSH), testosterone, and dehydroepiandrostenedione have improved significantly in all patients (p < 0.001 in all), the significant decrease in serum luteinizing hormone (LH), LH/ FSH ratio, and estrogen was only noted in patients with improved clinical response (p < 0.05, p < 0.001, and p < 0.001 respectively). CONCLUSION: Weight loss and improvements in hyperandrogenism following sleeve gastrectomy result in clinical and paraclinical improvement of PCOS signs and symptoms, including oligomenorrhea and ovulation induction.

Causal association between lipid-lowering drugs and female reproductive endocrine diseases: a drug-targeted Mendelian randomization study.

Purpose: The relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs. Methods: In this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility. Results: PCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p<0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p<0.05), but had no statistical impact on patients with oligomenorrhea. Conclusion: The findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea.

Are ABO/Rh blood groups A risk factor for polycystic ovary syndrome?

This study goaled to evaluate the ABO/Rh blood group distribution and its relationship with clinical and biochemical factors in polycystic ovary syndrome (PCOS) patients. ABO/Rh blood group distribution of the patients and the healthy individuals were compared. In addition, the features of clinical and biochemical factors were compared according to the ABO/Rh blood groups. Two hundred and sixty-five patients were involved in the study. At the time of diagnosis, hirsutism (86%) and oligomenorrhea (80.9%) were the most prevalent symptoms. There were 166 (62.6%) patients with baseline ultrasonography results consistent with PCOS. In 111 (41.9%) patients, insulin resistance was found. ABO blood group distributions in the patient (42.6% A, 17% B, 9.4% AB, 30.9% O) and control (42% A, 16% B, 8% AB, 34% O) groups were found to be similar (P = .9). There was no difference between oligomenorrhea, hirsutism, hair loss, acne, obesity, high androgen level, insulin resistance, and ultrasound characteristics according to ABO/Rh blood groups. In this study, ABO/Rh blood group distribution in individuals with PCOS was found to be similar to healthy individuals, and it was determined that ABO/Rh blood group was not a risk factor for PCOS. In addition, no correlation was found between the clinical and biochemical characteristics of the patients at the time of diagnosis and the ABO/Rh blood group.

Pre-polycystic ovary syndrome and polymenorrhoea as new facets of polycystic ovary syndrome (PCOS): Evidences from a single centre data set.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disorder with diverse metabolic implications. Diagnosis typically relies on oligo-amenorrhoea (OA), hyperandrogenism (HA), and polycystic ovarian morphology (PCOM). However, the role of polymenorrhoea in PCOS remains understudied. Additionally, limited information exists regarding metabolic disturbances in women with partial PCOS phenotypes that do not meet diagnostic criteria. This extensive database aims to provide substantial evidence on the metabolic implications of polymenorrhoea and partial PCOS phenotypes. DESIGN: Prospective observational study. PATIENTS AND MEASUREMENTS: In this single-centre study, 6463 women with PCOS-like characteristics and 3142 age-matched healthy women were included. The study compared clinical (anthropometry, modified Ferriman Gallwey [mFG] score), hormonal (serum testosterone), and metabolic (plasma glucose, serum lipids, insulin) characteristics between women diagnosed with PCOS, those with partial PCOS phenotypes, and the healthy control group RESULTS: In all, 5174 women met Rotterdam criteria for PCOS diagnosis, while 737 were classified as Pre-PCOS, including HA (n = 538), OA (n = 121), or PCOM (n = 78). Common clinical features included oligomenorrhoea (75.5%), hirsutism (82.9%), obesity (27.2%), hypertension (1.6%), metabolic syndrome (19.6%), and diabetes mellitus (5.6%). Women diagnosed with PCOS, HA only, and OA only exhibited higher average body mass index, plasma glucose levels (both fasting and 2 h after the oral glucose tolerance test), and lipid fractions in comparison to those with PCOM and the healthy controls. However, indices of insulin resistance were similar among women with PCOS, HA, PCOM, and OA, albeit higher than in the healthy controls. The polymenorrhoea subgroup (5.9%) had lower BMI and serum testosterone, but similar mFG score, plasma glucose, insulin, and lipid levels as the oligomenorrhoea subgroup. CONCLUSION: The metabolic disturbances observed in Pre-PCOS women highlight the need to reassess diagnostic criteria. Including the polymenorrhoea subcategory in PCOS criteria is recommended due to similar metabolic dysfunctions as the oligomenorrhoea group.

Effectiveness of Zhenqi Buxue Oral Liquid Combined with Progesterone for Treatment of Oligomenorrhea and Hypomenorrhea with Qi-Blood and Kidney (Shen) Essence Deficiency: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of Zhenqi Buxue Oral Liquid (ZQ), progesterone capsules, and their combination in treating oligomenorrhea and hypomenorrhea with qi-blood and Kidney (Shen) essence deficiency. METHODS: This was a prospective, randomized, multi-center controlled trial between June 2022 to December 2022. Ninety-six oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency were randomly assigned to receive ZQ (ZQ group, 29 cases), progesterone capsules (PG group, 32 cases), or the combined Chinese and Western medicine (COM group, 31 cases) at a ratio of 1:1:1. Patients in the ZQ or PG group took daily 10 mL twice a day of ZQ or 200 mg once a day of progesterone capsules for 10 consecutive days on day 15 of the menstrual cycle respectively, and patients in the COM group received the same ZQ combined with progesterone capsules. The treatment course lasted for 3 months and follow-up was performed at 1 and 3 months after the end of treatment. Primary endpoint was the menstrual Traditional Chinese Medicine Syndrome Scale (TCMSS) scores. Secondary endpoints included pictorial blood loss assessment chart (PBAC) scores, clinical efficacy rate, 36-item Short Form Health Survey (SF-36) scores, sex hormones and thickness of endometrium. Adverse events (AEs) were recorded. RESULTS: TCMSS scores after 1- and 3-month treatment in all groups were significantly lower than those at baseline (P<0.05). Only TCMSS scores after 3-month treatment in the ZQ and COM groups continuously decreased compared with those after 1-month treatment in the same group (P<0.01). TCMSS scores after 3-month treatment in the ZQ and COM groups were significantly lower than those in the PG group (P<0.05, P<0.01). Compared with baseline, PBAC scores in the ZQ and COM groups after 3 months of treatment were also significantly higher (both P<0.01). The total effective rates of TCM syndrome of 3-month treatment were significantly improved in all groups compared with that after 1 month of treatment (P<0.05). The total effective rate of the COM group was the highest in the 3rd month of treatment and significantly higher than that of PG group alone (P<0.05). Compared with baseline, only the SF-36 scores of COM group were significantly improved after 3 months of treatment (P<0.05). No serious adverse reactions were observed after treatment. CONCLUSIONS: The combination of ZQ and PG, or ZQ only had better effects on reducing TCMSS scores compared with PG, and COM showed the higher total effective rate compared with monotherapy. Besides, COM could effectively improve menstrual blood loss and quality of life. ZQ combined with PG may be an effective and safe option for oligomenorrhea and hypomenorrhea patients with qi-blood and Shen essence deficiency.

The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women's study.

In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.

The effect of Curcumin on metabolic parameters and androgen level in women with polycystic ovary syndrome: a randomized controlled trial.

BACKGROUND: Considering the high prevalence of polycystic ovary syndrome (PCOS) in women of reproductive age and the metabolic disorders associated with it, this study was conducted to determine the effects of curcumin on metabolic indices and androgen level (primary outcomes), and menstruation characteristics, and hirsutism (secondary outcomes) in women with PCOS. METHODS: This triple-blind randomized controlled trial was conducted on women with PCOS who visited the health centers at Eslamshahr County (Tehran Province-Iran) from 2020 to 2022. The participants were allocated into two groups (curcumin and placebo) using block randomization method. The treatment group received two 500 mg edible curcumin tablets together at the same time per day for twelve weeks while the control group received placebo tablets similar to curcumin. Biochemical parameters such as Fasting Blood Insulin (FBI), Fasting Blood Sugar (FBS), triglyceride, total cholesterol, Low Density Lipoprotein- cholesterol (LDL-C), High Density Lipoprotein- cholesterol (HDL-C) were measured before intervention and then 3 months after the intervention. Sex Hormone Binding Globulin (SHBG) and testosterone serum levels were measured 3 months after the intervention. Questionnaires regarding the menstrual cycle characteristics and the Ferriman-Gallwey score were also filled for evaluating hirsutism before the intervention as well as 3 months after the intervention. The independent t-test, Mann-Whitney U test, and ANCOVA were used to analyze the data. RESULTS: There was no statistically significant difference between the two groups in terms of socio-demographic and the baseline levels of measured outcomes. After 12 weeks of intervention, the mean serum FBS levels in the curcumin group were significantly lower than in the placebo group (mean difference: 6.24; 95%confidence interval: -11.73 to -0.76; P = 0.027) but there was no significant difference between the two groups in terms of triglyceride (P = 0.351), cholesterol (P = 0.528), LDL (P = 0.064), HDL (P = 0.306), FBI (p = 0.929), SHBG (p = 0.682), and testosterone (p = 0.133) serum levels. After the intervention, amenorrhea and oligomenorrhea frequency in the curcumin group was significantly lower than in the placebo group (13% vs. 22%, P = 0.038). There was no significant difference in terms of duration of menstruation (P = 0.286) and hirsutism (P = 0.630) between the two groups. CONCLUSION: Curcumin decreased FBS levels and improved menstruation characteristics (amenorrhea, oligomenorrhea, and menstrual irregularities) in women with PCOS but did not affect other metabolic, hormonal, and hirsutism indices. More studies using a larger sample size are required for a definitive conclusion. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N51 Date of registration: 30/11/2019. URL: https://en.irct.ir/user/trial/40597/view ; Date of first registration: 30/11/2020.

Polycystic ovary syndrome v.2023: Simplified diagnostic criteria for an East Asian phenotype.

Introduction: Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary syndrome (PCOS). This has prompted the re-examination of the features that characterise this common condition. Current definitions have led to great heterogeneity in the prevalence of PCOS and have contributed to inconsistent treatment protocols and assessment of therapeutic outcomes. Diagnosis is further complicated by the lack of universal agreement on threshold cut-offs for ovarian dysfunction and ethnic differences in hirsutism; both of which are key features in the definitions that are commonly used currently. These challenges often result in dissatisfaction with medical care among PCOS patients and their physicians. Method: Our factor analysis mathematically identified anti-Mullerian hormone (AMH), associated polycystic ovarian morphology (PCOM) and serum testosterone as the only significant cluster associated with menstrual cycle length variability. Results and Conclusion: As such, we propose a simplified criteria wherein the presence of at least 2 of the 3 features below would be sufficient to define PCOS: (1) chronic oligo-ovulation or anovulation as indicated by oligomenorrhea (cycle lengths >35 days) or amenorrhea; (2) PCOM: raised AMH ≥37.0 pmol/L instead of transvaginal ultrasound assessment of ovaries; and (3) Androgen excess, or raised serum androgens above the laboratory reference for women. Further studies are required to examine whether the proposed criteria would reduce diagnostic confusion and improve care and outcomes, especially among patients of East Asian ethnicities.

Maternal polycystic ovarian syndrome and pubertal development in daughters and sons: a population-based cohort study.

STUDY QUESTION: Does maternal polycystic ovarian syndrome (PCOS) affect the timing of pubertal development in daughters and sons? SUMMARY ANSWER: Maternal PCOS was associated with earlier adrenarche in daughters. WHAT IS KNOWN ALREADY: Female adolescents with PCOS often experience earlier adrenarche compared to adolescents without PCOS, due to hyperandrogenism. Likewise, they usually have hyperandrogenism during pregnancy, which might potentially affect the development of the foetus, including its future reproductive health. STUDY DESIGN, SIZE, DURATION: In this population-based cohort study, we included 15 596 mothers-child pairs from the Danish National Birth Cohort (DNBC) Puberty Cohort, who were followed from foetal life until full sexual maturation or 18 years of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using register-based and self-reported information on maternal PCOS and menstrual irregularities, collected during pregnancy, we categorized the mothers as having PCOS (n = 251), oligomenorhoea (n = 134), 'other menstrual irregularities' (n = 2411) or no menstrual abnormalities (reference group, n = 12 800). The children provided self-reported information on pubertal development every 6 months from the age of 11 years. The main outcome measures were adjusted mean age differences (in months) at attaining several individual pubertal milestones using an interval-censored regression model, as well as the average difference in age at attaining all pubertal milestones combined into a single estimate using Huber-White robust variance estimation. MAIN RESULTS AND THE ROLE OF CHANCE: We found that maternal PCOS was associated with an accelerated pubertal development in daughters with an overall average difference of -3.3 (95% CI: -6.3; -0.4) months based on all pubertal milestones compared to the reference group. When further looking into the average difference for adrenarche only (pubarche, axillary hair and acne), the average difference was -5.4 (95% CI: -8.7; -2.1) months compared to the reference group; whereas thelarche and menarche did not occur earlier in daughters of mothers with PCOS (average difference: -0.8 (95% CI: -3.9; 2.4) months). Oligomenorrhoea and 'other menstrual irregularities' were not associated with pubertal development in daughters. Neither PCOS, oligomenorrhoea nor 'other menstrual irregularities' were associated with pubertal development in sons. LIMITATIONS, REASONS FOR CAUTION: We expect some degree of non-differential misclassification of maternal PCOS and menstrual irregularities as well as pubertal development in the children. WIDER IMPLICATIONS OF THE FINDINGS: Maternal PCOS might accelerate adrenarche in daughters. Whether this is due to genetics, epigenetics or prenatal programming by hyperandrogenism in foetal life remains unsolved. The results from the present study can be generalized to Caucasian populations. STUDY FUNDING/COMPETING INTEREST(S): The study is funded by the Faculty of Health at Aarhus University. The authors have no financial relationships or competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of Hormonal Profile and Ovarian Morphology among Adolescent Girls with Menstrual Irregularities in a Tertiary Care Centre at Central India.

Menstrual disturbances are common among adolescents with a prevalence rate of 11.3-26.7%. The most frequent menstrual irregularities are oligomenorrhea, menorrhagia, polymenorrhoea, and hypomenorrhea. PCOS (polycystic ovarian syndrome) is now recognized as the most prevalent endocrine disorder among the women of reproductive age. The current study was planned to evaluate socio-demographic factors, endocrine profiles, and ovarian morphology among adolescent girls with menstrual irregularities and compare these parameters in different phenotypes of adolescent PCOS cases. It is a hospital-based cross-sectional study among 248 adolescent girls (10-19 years) with menstrual irregularities. After obtaining informed consent, history and clinical examination findings were recorded on preform proforma. All girls were assessed on day 2/3 of the menstrual cycle for hormonal profile (serum TSH, FSH, LH, prolactin, and serum testosterone) and ovarian morphology (by transabdominal ultrasonography). All participating girls were divided into three groups (groups 1, 2, and 3) corresponding to phenotypes A, B, & D as per the Rotterdam criteria. In the study, oligomenorrhea was the most common menstrual disorder (70.97%). Biochemical hyperandrogenism and thyroid dysfunction were reported in 14.91% and 8.46% of girls, respectively. Our study noted that phenotype D ,i.e., group 3 (MI + PCOM-HA; 49.43%) was the most common phenotype in the study. In a comparative analysis of different groups, significant differences (p < 0.05) in hormonal and metabolic parameters showed highest in group 2, which represents phenotype B of PCOS (hyperandrogenic anovulation). This analysis revealed that adolescent hyperandrogenism (phenotypes A and B) is associated with a more deranged hormonal and metabolic profile than nonandrogenic PCOS (phenotype D). To prevent long-term sequelae, lifestyle changes, early treatment, and close follow-up are recommended in this subset of girls.

Efficacy and safety of acupuncture on oligomenorrhea due to polycystic ovary syndrome: An international multicenter, pilot randomized controlled trial.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common disorders of reproductive endocrinology affecting women of reproductive age. Our study aims to explore the feasibility of a full-scale trial to evaluate the efficacy and safety of acupuncture for PCOS. METHODS: This study is a two-armed, parallel, multi-country, multi-center, pilot randomized controlled trial (RCT) for PCOS with oligomenorrhea. We will recruit 60 women aged 20 to 40 years with oligomenorrhea due to PCOS. The participants will be randomly assigned to acupuncture and control groups. The acupuncture group will undergo a total of 40 sessions for 16 weeks with usual care. The control group will be managed with usual care (regular meals, sufficient sleep, and appropriate exercise) only. The primary clinical outcome is mean change in menstrual frequency from baseline to 16 weeks and 32 weeks (follow-up) after the start of the trial. The secondary outcomes are menstrual period, levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and total testosterone, LH/FSH ratio, antral follicle count and ovarian volume, body mass index, waist hip ratio, acne severity, and health-related quality of life questionnaire scores at 16 and 32 weeks after the start of the trial. DISCUSSION: This is the first protocol for multi-country, multi-center RCTs for PCOS in Korea and China. The control group in this study will be subjected to usual care (regular meals, enough sleep, and appropriate exercise). The results of this study will provide evidence for future clinical decisions and guidelines.This trial has been registered at ClinicalTrials.gov (Identifier: NCT04509817).

Effect of the presence of polycystic ovary syndrome-related features on anti-Mullerian hormone and androstenedione levels in adolescents with or without menstrual irregularity.

PURPOSE: To determine the variation in anti-Mullerian hormone (AMH) and androstenedione (A4) concentrations in adolescent girls, with or without menstrual cycle disorder in relation to phenotypic features of. PCOS. METHODS: Adolescent girls (n = 129), age range 14-19 years, were recruited in the cohort study. All participants were in the 4th or 5th year after menarche. Sixty-eight had menstrual irregularities, usually oligomenorrhea (OM), and 61 had regular menstruation (RM). AMH and A4 concentrations were measured. Hirsutism was recorded. Polycystic ovarian morphology (PCOM) was evaluated by transabdominal pelvic ultrasonography. Polycystic ovary syndrome (PCOS) features were defined according to Rotterdam consensus criteria. RESULTS: AMH and A4 were significantly higher in adolescent girls with OM than in girls with RM (p < 0.05). A4 and body mass index (BMI) of adolescents with OM was significantly higher in those with hirsutism than those without hirsutism (p = 0.01 and 0.008, respectively). There was a positive correlation between A4 and BMI (r: 0.327, p < 0.01). Logistic regression showed that the frequency of OM in the presence of PCOM was 10.8 times (95% CI 2.04-12.09) compared to those without PCOM. The highest AMH concentrations were found in girls with OM, hirsutism, and PCOM (p < 0.05). CONCLUSIONS: AMH and A4 are elevated in adolescents with oligomenorrhoea. High A4 is more prominent in the presence of hirsutism and is associated with increased BMI. PCOM, increases the likelihood of oligomenorrhea by about 10 times. AMH increase as the combination of clinical features of PCOS increases in adolescents with menstrual irregularity.

Association of severity of menstrual dysfunction with hyperinsulinemia and dysglycemia in polycystic ovary syndrome.

STUDY QUESTION: Is the severity of menstrual cyclicity related to hyperinsulinemia and dysglycemia in women with hyperandrogenic polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Hyperandrogenic PCOS women with amenorrhea, compared to those with oligomenorrhea or eumenorrhea, had a greater risk of post-challenge hyperinsulinemia, which may explain their higher prevalence of dysglycemia. WHAT IS KNOWN ALREADY: PCOS is associated with metabolic dysregulation including insulin resistance (IR) and hyperinsulinemia, risk factors for type 2 diabetes mellitus (T2DM) and other vascular-metabolic morbidities. Although the severity of menstrual cyclicity is associated with IR in PCOS, it is unclear whether, and to what extent, it is related to hyperinsulinemia and glycemic abnormalities. STUDY DESIGN, SIZE, DURATION: We prospectively compared the degree of menstrual cyclicity with the presence of dysglycemia (elevated 1-h plasma glucose ≥155 mg/dl; abnormal glucose tolerance [AGT], including prediabetes and T2DM; and AUC for glucose [G-AUC]) or dynamic state hyperinsulinemia (peak insulin levels either at 1 or 2 h of the oral glucose tolerance test (oGTT) and AUC for insulin [I-AUC]) in 333 hyperandrogenic PCOS women. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a tertiary care setting, hyperandrogenic PCOS participants with ovulatory eumenorrhea (Ov-Eumeno, n = 25), anovulatory eumenorrhea (Anov-Eumeno, n = 33), oligomenorrhea (Oligo, n = 150) and amenorrhea (Ameno, n = 125) underwent comprehensive phenotyping and a 2-h 75 g oGTT. MAIN RESULTS AND THE ROLE OF CHANCE: Mean BMI was greater among Ameno women than among Oligo, Anov-Eumeno or Ov-Eumeno women. Adjusting for BMI, the Ameno group demonstrated higher mean 1- and 2-h insulin and glucose, peak insulin and I-AUC and G-AUC, and either had a higher, or tended toward having a higher, prevalence of elevated 1-h glucose level and prevalence of AGT than the Oligo, Anov-Eumeno or Ov-Eumeno groups. In logistic regression, adjusting for BMI, Ameno women were more likely to have: AGT than Oligo women (odds ratio [OR]: 2.3; 95% CI: 1.3 to 4.2); elevated 1-h glucose (OR: 10.2; CI: 1.3-79.7) than those with Ov-Eumeno; and both AGT (OR: 1.7; CI: 1.1-2.6) and elevated 1-h glucose (OR: 1.8; CI: 1.1-2.8) than those with Anov-Eumeno or Ov-Eumeno when combined. Race/ethnicity, age, waist-to-hip ratio, fasting insulin and glucose, and biochemical or clinical measures of hyperandrogenism were similar across the four menstrual categories. LIMITATIONS, REASONS FOR CAUTION: Our study was limited by its cross-sectional nature and by studying women affected by PCOS as defined by the Androgen Excess & PCOS Society criteria (i.e. Rotterdam Phenotypes A, B and C) who were identified in the clinical setting. Consequently, extrapolation of the present data to other PCOS phenotypes (e.g. PCOS Phenotype D) should be made with caution. WIDER IMPLICATIONS OF THE FINDINGS: In hyperandrogenic PCOS phenotypes, a history of amenorrhea, compared to oligomenorrhea or eumenorrhea, suggests a more severe cardiometabolic risk, including a higher degree of hyperinsulinemia and greater prevalence of glycemic abnormalities. These findings may assist in refining the treatment and screening guidelines for glycemic abnormalities in PCOS. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by grants R01-DK073632 and R01-HD29364 from the NIH and an endowment of the Helping Hand of Los Angeles, Inc. (to R.A.). M.D.P. has no competing interests to declare. U.E. is an investor in Concentric Analgesics, Inc. R.A. serves as a consultant for Spruce Biosciences and Fortress Biotech and an advisor for Aurora Forge. TRIAL REGISTRATION NUMBER: N/A.

Sharma's parachute sign a new laparoscopic sign in abdomino pelvic tuberculosis.

AIMS: To demonstrate a new laparoscopic sign "Sharma's Parachute sign" in abdominopelvic tuberculosis in women with infertility. METHODS: A total of 104 women who were diagnosed to have abdominopelvic tuberculosis, on endometrial sampling or on laparoscopy were enrolled in this ongoing study on tuberculosis in infertility. A new laparoscopic "Sharma's parachute sign" was looked for in these cases on laparoscopy. RESULTS: The mean age, pairty and duration of infertility was 27.6 years, 0.58 and 4.1 years respectively. Menstrual dysfuction were common especially hypomenorrhoea (34.61%), oligomenorrhoea (36.53%) along with constitutional symptoms and abdomino pelvic pain or lump. Diagnosis of abdominopelvic tuberculosis was made by identification of acid fast bacilli (AFB) on microscopy or culture of endometrial aspirate or peritoneal biopsy or positive gene Xpert or positive polymerase chain reaction (PCR) or histopathological demonstration of epithelioid granuloma on endometrial or peritoneal biopsy, various laparoscopic findings on pelvic and abdominal organs were tubercles and shaggy areas (white deposits, caseous nodules encysted ascites, abdominal and pelvic adhesions, tubal findings (hydrosalpinx, pyosalpinx, beaded or calcified tubes). A new "Sharma's parachute sign"in which ascending colon was totally adherent to anterior abdominal wall with its mesocolon looking like an open parachute with small caseous nodule was seen in 11 (10.5%) cases. CONCLUSION: Diagnostic laparoscopy is an important investigation for abdominopelvic tuberculosis showing various adhesions including new parachute sign.

SHBG as a Marker of NAFLD and Metabolic Impairments in Women Referred for Oligomenorrhea and/or Hirsutism and in Women With Sexual Dysfunction.

PCOS is one of the most common endocrine disorders and NAFLD is one of its most dangerous metabolic consequences. The diagnosis of NAFLD is not a practical task and the condition is at risk of being overlooked. The use of simpler but still reliable surrogate markers is necessary to identify women with a high likelihood of NAFLD. The aim of this study was to evaluate the clinical correlates of NAFLD Liver Fat Score (NAFLD-LFS) in women with oligomenorrhea and/or hirsutism. Furthermore, the study aimed to evaluate whether, among the hormonal parameters evaluated in such women, possible hallmarks of NAFLD may be identified. To this purpose, 66 women who attended our Outpatient Clinic for oligomenorrhea and/or hyperandrogenism were included in the study. In order to validate the results obtained in the first cohort, a second independent sample of 233 women evaluated for female sexual dysfunction (FSD) was analyzed. In cohort 1, NAFLD-LFS positively correlated with metabolic and inflammatory parameters. Among the hormone parameters, NAFLD-LFS showed no significant relationships with androgens but a significant negative correlation with SHBG (p<0.0001) that therefore appeared as a candidate hallmark for pathologic NAFLD-LFS. The ROC analysis showed a significant accuracy (81.1%, C.I.69.1-93.0, p <0.0001) for SHBG in identifying women with a pathological NAFLD-LFS. In particular, a SHBG 33.4 nmol/l was recognized as the best threshold, with a sensitivity of 73.3% and a specificity of 70.7%. In order to validate this SHBG as a marker of metabolic impairment possible related with the presence of NAFLD, we tested this threshold in cohort 2. FSD women with SHBG <33.4 nmol/l had worse metabolic parameters than women with SHBG ≥33.4 nmol/l and a significantly higher NAFLD-LFS even after adjusting for confounders (B=4.18 [2.05; 6.31], p=0.001). In conclusion, this study provides a new evidence in the diagnostic process of NAFLD, showing that the measurement of SHBG, which is routinely assessed in the workup of women referred for possible PCOS, could identify women at higher metabolic risk, thus detecting those who may deserve further targeted diagnostic assessment.

A large ovarian steroid cell tumor-not otherwise specified with a unique combination of benign and malignant features as a challenging cause of oligomenorrhea and hirsutism in a 21-year-old Syrian female: a case report.

BACKGROUND: Ovarian steroid cell tumors represent a rare category of sex cord-stromal tumors that constitute less than 0.1% of all ovarian tumors. These neoplasms are classified into three main subtypes according to the cell of origin: Leidyg cell tumors, stromal luteomas, and steroid cell tumors not otherwise specified (SCTs-NOS). The latter subtype is defined as a neoplasm of an uncertain lineage that mostly affects middle-aged women, whereas it's rare in younger ages. CASE PRESENTATION: We report a case of a 21-year-old virgin female who presented to our hospital with complaints of mild abdominal pain, hirsutism, and oligomenorrhea for more than a year. Before her current admission, the patient had attended an external gynecologic clinic where she had been prescribed oral contraceptives to regulate her periods. Nevertheless, on presentation to our institution, physical examination revealed abdominal tenderness with a palpable pelvic mass and mild hirsutism in the thigh. Ultrasonography demonstrated a large left ovarian mass measuring 154 × 104 mm, and compressing the uterus. Therefore, a unilateral salpingo-oophorectomy was performed, and interestingly, pathologic examination of the large aforementioned mass alongside with immunohistochemical correlation revealed the diagnosis of a large ovarian steroid cell tumor-not otherwise specified with a unique combination of benign and malignant features. CONCLUSIONS: Although ovarian steroid cell tumors represent a rare category, they must be considered in the differential diagnosis for mild virilization symptoms in young females due to the importance of early diagnosis and management. In this manuscript, we aimed to present the first case report from Syria that highlights the crucial role of detailed morphological examination for challenging cases despite the difficulties in differential diagnosis, and the absence of ancillary techniques. Furthermore, we managed to discuss a brief review of diagnostic methods, histological characteristics, and treatment recommendations.