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.

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.

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.

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.

Fallo ovárico, una problemática para las mujeres en edad reproductiva y su relación genética / Ovarian failure, a problem for women in reproductive age and its genetic relationship

La insuficiencia ovárica primaria es una condición en la que las mujeres menores de 40años experimentan oligomenorrea o amenorrea durante 4meses o más; esta pérdida temprana de la función ovárica puede estar relacionada con una serie de etiologías, incluidos trastornos genéticos, autoinmunes, infecciones o causas iatrogénicas; no obstante, del 74 al 90% son idiopáticas. A pesar de ser una alteración poco prevalente, es de gran importancia clínica, ya que afecta en múltiples aspectos de la vida a todas las mujeres. En la actualidad se están desarrollando diferentes estudios con el fin de encontrar nuevos blancos moleculares para establecer nuevas terapias para el tratamiento de esta patología.(AU)

Primary ovarian failure is a condition in which women under 40 experience oligomenorrhea or amenorrhea for 4months or longer; this early ovarian function loss may be related to a series of etiologies, including genetic disorders, autoimmune diseases, infections or iatrogenic causes; however 74%-90% are idiopathic. Despite being a less prevalent disorder, it is of great clinical importance since it affects all women in multiple aspects of life. At present, different studies are being developed in order to find new molecular targets to establish new therapies for the treatment of this pathology.(AU)

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.

Amenorrhea and oligomenorrhea risk related to exercise training volume and intensity: Findings from 3705 participants recruited via the STRAVA™ exercise application.

OBJECTIVES: To investigate associations between self-reported exercise training habits and amenorrhea/oligomenorrhea among physically active women. DESIGN: A cross-sectional survey was completed by 3705 women (median age = 40 years [quartile 1, quartile 3: 30, 45], body mass index = 22.1 kg/m2 [20.5, 24.2]) representing multiple nationalities and sports via the STRAVA™ exercise application. Respondents selected the amount of time they participated in low intensity, moderate intensity, and high intensity exercise training per week. Amenorrhea/oligomenorrhea was defined as self-reporting ≤10 menses in the last year. METHODS: Associations between weekly exercise volume for low intensity training, moderate intensity training, and high intensity training and amenorrhea/oligomenorrhea were modeled with univariate logistic regression models, followed by adjustment for age and body mass index. RESULTS: Amenorrhea/oligomenorrhea prevalence was 16 % (n = 576/3705), with no difference by country of origin or most sport modes. In adjusted models, participating in low intensity training ≥7 h/week or moderate intensity training ≥6 h/week was associated with 1.43 (95 % confidence interval: 1.04-1.96) and 1.46 (1.10-1.95) greater odds of amenorrhea/oligomenorrhea compared to 2 to 3 h/week, respectively. Similarly, high intensity training ≥5 h/week was associated with 1.41 (1.03-1.92) greater odds of amenorrhea/oligomenorrhea compared to 1 to 2 h/week. Participating in low intensity training for ≤30 min/week compared to 2 to 3 h/week was associated with reduced amenorrhea/oligomenorrhea odds (0.65 [0.44-0.94]). CONCLUSIONS: Taken together, these associations suggest greater weekly exercise volume, irrespective of intensity, may increase amenorrhea/oligomenorrhea risk among physically active women.

COVID-19 vaccination and menstrual disorders among women: Findings from a meta-analysis study.

BACKGROUND: COVID - 19 vaccine can lead to various local and systemic side effects, including menstrual irregularities in women. There is no robust quantitative evidence of the association between the COVID - 19 vaccine and menstrual irregularities. A meta-analysis was performed to estimate the pooled prevalence of a range of menstrual disorders that may occur in women following COVID - 19 vaccination. METHODS: After searching for epidemiological studies, we systematically performed a meta-analysis on PubMed/Medline, EMBASE, and Science Direct. Sixteen studies were finally included in the study. We estimated the pooled prevalence and corresponding 95 % confidence intervals (CIs) for a group of menstrual disorders, including menorrhagia, polymenorrhea, abnormal cycle length, and oligomenorrhea. Heterogeneity was assessed using the I2 statistic and the Q test. RESULTS: Overall, the pooled prevalence of menorrhagia was 24.24 % (pooled prevalence 24.24 %; 95 % CI: 12.8-35.6 %). The pooled prevalence of polymenorrhea was 16.2 % (pooled prevalence: 16.2 %; 95 % CI: 10.7-21.6 %). The pooled prevalence of abnormal cycle length was relatively lower than that of the other disorders (pooled prevalence: 6.6 %; 95 % CI: 5.0-8.2 %). The pooled prevalence of oligomenorrhea was 22.7 % (95 % CI: 13.5-32.0 %). CONCLUSION: The findings indicate that menorrhagia, oligomenorrhea, and polymenorrhea were the most common menstrual irregularities after vaccination. The findings also suggest that a relatively high proportion of women suffer from menstrual irregularities. Further longitudinal studies are needed to confirm the causal relationship between COVID-19 vaccination and menstrual irregularities.

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.

Patients with DeSanto-Shinawi syndrome: Further extension of phenotype from Italy.

Here we describe three patients with neurodevelopmental disorders characterized by mild-to-moderate intellectual disability, mildly dysmorphic features, and hirsutism, all of which carry de novo sequence variants in the WW domain-containing adaptor of the coiled-coil (WAC) gene; two of these-c.167delA, p.(Asn56I1efs*136) and c.1746G>C, p.(Gln582His)-are novel pathogenic variants, and the third-c.1837C>T, p(Arg613*)-has been previously described. Diseases associated with WAC include DeSanto-Shinawi syndrome; to date, de novo heterozygous constitutional pathogenic WAC variants have caused a syndromic form of intellectual disability and mild dysmorphic features in 33 patients, yet potential associations with other clinical manifestations, such as oligomenorrhea and hyperandrogenism, remain unknown, because the phenotypic spectrum of the condition has not yet been delineated. The patient bearing the novel c.167delA WAC gene variant presented a normal psychomotor development, oligomenorrhea, hyperandrogenism, and hirsutism, and hirsutism was also observed in the patient with the c.1746G>C WAC gene variant. Hypertrichosis and hirsutism have been described in nine DeSanto-Shinawi patients, only in 17 of the 33 aforementioned patients thus far reported this aspect, and no hormonal-pattern data are available. In conclusion, we note that the pathogenic c.167delA WAC variant may be associated with a mild phenotype; and in addition to the neurodevelopmental problems nearly all DeSanto-Shinawi patients experience (i.e., intellectual disability and/or developmental delay), we recommend the addition of mild dysmorphic features, hirsutism, and hypertrichosis to this clinical presentation.

The Prevalence of Menstrual Cycle Disorders in Female Athletes from Different Sports Disciplines: A Rapid Review.

The aim of this study was to rapidly review the literature on the prevalence of menstrual disorders in female athletes from different sports modalities. Articles were searched in the Web of Science and PubMed database in May 2022. A total of 1309 records were identified, and 48 studies were included in the final stage. The menstrual disorders described in the included studies were primary (in 33% of included studies) and secondary amenorrhea (in 73% of included studies) and oligomenorrhea (in 69% of included studies). The prevalence of menstrual disorders among the studies ranged from 0 to 61%. When data were pooled according to discipline (mean calculation), the highest prevalence of primary amenorrhea was found in rhythmic gymnastics (25%), soccer (20%) and swimming (19%); for secondary amenorrhea in cycling (56%), triathlon (40%) and rhythmic gymnastics (31%); and oligomenorrhea in boxing (55%), rhythmic gymnastics (44%) and artistic gymnastics (32%). Based on the results of this review, the study supports the literature of the higher prevalence of menstrual disorders in gymnastics and endurance disciplines. However, team sports modalities such as volleyball and soccer also presented a considerable percentage of menstrual disorders compared to the general population. It reinforces the importance of coaches and physicians paying attention to athletes' menstrual cycle as the occurrence of menstrual disorders can be associated with impairment on some health components.

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.

Bone mineral density in response to increased energy intake in exercising women with oligomenorrhea/amenorrhea: the REFUEL randomized controlled trial.

BACKGROUND: Energy deficiency can result in menstrual disturbances and compromised bone health in women, a condition known as the Female Athlete Triad. OBJECTIVES: The REFUEL randomized controlled trial assessed the impact of increased energy intake on bone health and menstrual function in exercising women with menstrual disturbances. METHODS: Exercising women with oligomenorrhea/amenorrhea (Oligo/Amen) were randomly assigned to an intervention group (Oligo/Amen + Cal, n = 40, mean ± SEM age: 21.3 ± 0.5 y; weight: 55.0 ± 1.0 kg; BMI: 20.4 ± 0.3 kg/m2) who increased energy intake 20%-40% above baseline energy needs for 12 mo or a control group (Oligo/Amen Control, n = 36; mean ± SEM age: 20.7 ± 0.5 y; weight: 59.1 ± 1.3 kg; BMI: 21.3 ± 0.4 kg/m2). Energy intake and expenditure, metabolic and reproductive hormones, body composition, and areal bone mineral density (aBMD) were assessed. RESULTS: Oligo/Amen + Cal improved energy status [increased body mass (2.6 ± 0.4 kg), BMI (0.9 ± 0.2 kg/m2), fat mass (2.0 ± 0.3 kg), body fat percentage (2.7% ± 0.4%), and insulin-like growth factor 1 (37.4 ± 14.6 ng/mL)] compared with Oligo/Amen Control and experienced a greater likelihood of menses (P < 0.05). Total body and spine aBMD remained unchanged (P > 0.05). Both groups demonstrated decreased femoral neck aBMD at month 6 (-0.006 g/cm2; 95% CI: -0.011, -0.0002 g/cm2 ; time main effect P = 0.043) and month 12 (-0.011 g/cm2; 95% CI: -0.021, -0.001 g/cm2; time main effect P = 0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (-0.006 g/cm2; 95% CI: -0.011, -0.002 g/cm2; time main effect P = 0.004). CONCLUSIONS: Although higher dietary energy intake increased weight, body fat, and menstrual frequency, bone mineral density was not improved, compared with the control group. The 12-mo intervention may have been too short and the increase in energy intake (∼352 kcal/d), although sufficient to increase menstrual frequency, was insufficient to increase estrogen or improve aBMD. Future research should refine the optimal nutritional and/or pharmacological interventions for the recovery of bone health in athletes and exercising women with Oligo/Amen.This trial was registered at clinicaltrials.gov as NCT00392873.

Health-related quality of life and menstrual problems in adolescents.

AIM: To evaluate whether the health-related quality-of-life (HRQoL) scores would be different for adolescents with menstrual problems as compared to those with normal menstruation after taking into account clinical, socio-demographic and life-style factors. METHODS: The Paediatric Quality of Life Inventory 4.0 scale was used to assess HRQoL in 126 schoolgirls of 16 ± 0.4 years old. The adolescents completed semi-structured questionnaires containing information on social and demographic characteristics, life-style features and menstrual questionnaires that included the following: age of menstruation, menstrual cycle length, duration of production, the number of pads used per day, menstrual pain and drug administration to relieve dysmenorrhea. The menstrual problems were classified into three main groups: dysmenorrhoea, oligomenorrhoea, and heavy menstrual bleeding. Anthropometric measurements were performed by a physician. Medical history was obtained from school medical charts. RESULTS: Ninety-seven (77%) girls had menstrual problems. Dysmenorrhoea (n = 92, 73%) was the most frequent of these, followed by oligomenorrhoea (n = 13, 10.3%) and heavy menstrual bleeding (n = 6, 4.8%). Thirteen (10.3%) girls had combined disorders. A multivariate analysis adjusted for life-style factors found an independent association of any menstrual problems, oligomenorrhoea and dysmenorrhoea with low HRQoL scores in the emotional functioning domain. For adolescents with oligomenorrhoea, an association with low total scale scores was also shown but it did not reach statistical significance. CONCLUSION: The prevalence of menstrual problems is high among schoolgirls. Medical professionals working with adolescents should know that girls with menstrual problems are highly likely to have a poor quality of life, especially those with oligomenorrhoea.

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.