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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/m(2)) 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/m(2)). 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/m(2)), 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). Both groups demonstrated decreased femoral neck aBMD at month 6 (−0.006 g/cm(2); 95% CI: −0.011, −0.0002 g/cm(2) ; time main effect P = 0.043) and month 12 (−0.011 g/cm(2); 95% CI: −0.021, −0.001 g/cm(2); time main effect P = 0.023). Both groups demonstrated a decrease in total hip aBMD at month 6 (−0.006 g/cm(2); 95% CI: −0.011, −0.002 g/cm(2); 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.

STUDY QUESTION Does increased daily energy intake lead to menstrual recovery in exercising women with oligomenorrhoea (Oligo) or amenorrhoea (Amen)? SUMMARY ANSWER A modest increase in daily energy intake (330 ± 65 kcal/day; 18 ± 4%) is sufficient to induce menstrual recovery in exercising women with Oligo/Amen. WHAT IS KNOWN ALREADY Optimal energy availability is critical for normal reproductive function, but the magnitude of increased energy intake necessary for menstrual recovery in exercising women, along with the associated metabolic changes, is not known. STUDY DESIGN, SIZE, DURATION The REFUEL study (trial # NCT00392873) is the first randomised controlled trial to assess the effectiveness of 12 months of increased energy intake on menstrual function in 76 exercising women with menstrual disturbances. Participants were randomised (block method) to increase energy intake 20–40% above baseline energy needs (Oligo/Amen + Cal, n = 40) or maintain energy intake (Oligo/Amen Control, n = 36). The study was performed from 2006 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were Amen and Oligo exercising women (age = 21.0 ± 0.3 years, BMI = 20.8 ± 0.2 kg/m2, body fat = 24.7 ± 0.6%) recruited from two universities. Detailed assessment of menstrual function was performed using logs and measures of daily urinary ovarian steroids. Body composition and metabolic outcomes were assessed every 3 months. MAIN RESULTS AND THE ROLE OF CHANCE Using an intent-to-treat analysis, the Oligo/Amen + Cal group was more likely to experience menses during the intervention than the Oligo/Amen Control group (P = 0.002; hazard ratio [CI] = 1.91 [1.27, 2.89]). In the intent-to-treat analysis, the Oligo/Amen + Cal group demonstrated a greater increase in energy intake, body weight, percent body fat and total triiodothyronine (TT3) compared to the Oligo/Amen Control group (P LIMITATIONS, REASONS FOR CAUTION While we had a greater than expected dropout rate for the 12-month intervention, it was comparable to other shorter interventions of 3–6 months in duration. Menstrual recovery defined herein does not account for quality of recovery. WIDER IMPLICATIONS OF THE FINDINGS Expanding upon findings in shorter, non-randomised studies, a modest increase in daily energy intake (330 ± 65 kcal/day; 18 ± 4%) is sufficient to induce menstrual recovery in exercising women with Oligo/Amen. Improved metabolism, as demonstrated by a modest increase in body weight (4.9%), percent body fat (13%) and TT3 (16%), was associated with menstrual recovery. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the U.S. Department of Defense: U.S. Army Medical Research and Material Command (Grant PR054531). Additional research assistance provided by the Penn State Clinical Research Center was supported by the National Center for Advancing Translation Sciences, National Institutes of Health, through Grant UL1 TR002014. M.P.O. was supported in part by the Loretta Anne Rogers Chair in Eating Disorders at University of Toronto and University Health Network. All authors report no conflict of interest. TRIAL REGISTRATION NUMBER NCT00392873 TRIAL REGISTRATION DATE October 2006 DATE OF FIRST PATIENT’S ENROLMENT September 2006

Background Current evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features. Methods Cross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women’s Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p Results Mean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status. Conclusion Energy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.

Context Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated. Objective To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood. Design and Setting A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997. Participants and interventions AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study. Results AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) μg/L (P Conclusions Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice.

In this study, we aimed to investigate the relationship between body mass index (BMI), waist circumference (WC) or waist-to-hip ratio (WHR) and oligomenorrhea or irregular menstruation in Chinese women of childbearing age. A total of 1,423 Han women aged 19–39 years who were routinely examined at the Physical Examination Center of Peking University People's Hospital were enrolled by convenience sampling method. All participants were asked to fill up menstrual questionnaires. Binary logistic regression models were used to assess the odds ratio (OR) of different BMI, WC and WHR groups for the prevalence of oligomenorrhea and irregular menstruation. Moreover, we used the ROC curves to compare the predictive effects of BMI, WC and WHR on oligomenorrhea and irregular menstruation. Among the 1,423 participants, 93 women (6.5%) had BMI ≥ 30 kg/m2, 6.5% of the participants had oligomenorrhea, and 22.6% had irregular menstrual menstruation. Overall, those with BMI ≥30 kg/m2 (OR = 2.543; 95%CI 1.332–4.856; p = .005) or WC ≥ 90 cm (OR = 2.023; 95%CI 1.198–3.416; p = .008) were more likely to have long menstrual cycle. The prevalence of irregular menstruation was higher in the BMI ≥30 kg/m2 (OR = 2.509; 95%CI 1.591–3.958; p < .001), WC ≥ 90 cm (OR = 2.299; 95%CI 1.619–3.265; p < .001) and WHR ≥ 0.86 (OR = 1.739; 95%CI 1.293–2.339; p < .001) groups. The ROC curve showed that all three anthropometric indices had predictive effect, while there was no significant difference in predicting oligomenorrhea. WC was a better predictor for irregular menstruation compared with BMI. Obesity, oligomenorrhea and irregular menstruation were common in Chinese women of childbearing age, and obesity was associated with oligomenorrhea and irregular menstruation. Abdominal obesity might have a stronger predictive effect on irregular menstruation.

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.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.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).

Background: Adiposity rebound (AR), the second BMI rise in childhood at around the age of 6 years, is associated with obesity and metabolic alteration in later life. Given that polycystic ovary syndrome (PCOS) has a strong metabolic component, early life growth patterns could reveal a risk of PCOS. Thus, we aimed to investigate the associations between age at AR and PCOS diagnosis and BMI later in life. Materials and methods: This study is part of a prospective, population-based longitudinal study, where women with PCOS diagnosis by age 46 (n = 280) were compared with asymptomatic women (CTRLs, n = 1573). Weight and height data from birth to age 13 years, at age at menarche, and at ages 31 and 46 years were analyzed Results: Women with PCOS had lower birth weight (3357 +/- 477 vs. 3 445 +/- 505 g, p

To explore the independent role of age at menarche on menstrual abnormalities among adolescents. The present study was a multicenter cross-sectional study on a large sample (n = 3782) of Italian girls aged 13–21 y attending secondary school who already had menarche. Girls were asked to fill in a questionnaire on menarcheal age and menstrual features during the latest three menses. The gynecological age was computed as the difference between age at the survey and the age at menarche. Main outcome measures were: prevalence of oligomenorrhea, polymenorrhea, menstrual cycle irregularity, abnormal bleeding length and dysmenorrhea. Irregularity in the recent past and since menarche was also studied. Multiple logistic models were used to identify any independent association between each abnormal feature and age at menarche or gynecological age. Adjusted ORs and 95%CI were performed. After adjusting for covariates, menarcheal age was not independently associated with polymenorrhea (OR = 0.81; 95%CI 0.63–1.04), oligomenorrhea (OR = 1.16; 95%CI 0.94–1.43), menstrual cycle irregularity (OR = 0.99; 95%CI 0.86–1.14), abnormal bleeding length (OR = 0.96; 95%CI 0.87–1.06) and dysmenorrhea (OR = 1.03; 95%CI 0.85–1.24). The multivariate analysis suggests that the higher prevalence of oligomenorrhea and menstrual cycle irregularity among the girls who were older at menarche might be purely explained by their younger gynecological age. No evidence of any independent influence of age at menarche on menstrual abnormalities among young girls was shown by the investigation. The findings suggest that, after menarche, adolescent girls’ menstrual health should be checked to monitor the endocrine system maturation and to early intercept latent disorders becoming symptomatic.

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

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.

Polycystic ovarian syndrome is the most common endocrinological disorder in women of reproductive age and has a considerable metabolic, reproductive, and cardiovascular consequences. This study was designed to provide an overview of the presentation of he clinical profile and hormonal presentation of the patients with polycystic ovarian syndrome attending a tertiary care hospital.A descriptive cross-sectional study was conducted between September 14, 2019 to October 16, 2019 on patients presenting to a tertiary care hospital, after obtaining ethical clearance from Institutional Review Committee (Dated 03/09/2019) and informed consent from the patient or patient relatives. Data entry and analysis were done in Microsoft Excel 10. The data was statistically analysed using Statistical Package for the Social Sciences (SPSS) version 20.0.The study included 100 PCOS patients. The mean age of the patients was 24.9±4.52 years and the most common group was 26-34 years. The most common presenting symptom was menstrual irregularity which was seen in 86 (86%) of the patients, followed by weight gain in 55 (55%) of the patients. Thirty percent (30 in number) of the patients were overweight, while eleven (11%) of the patients had grade I obesity. LH/FSH ratio was more than or equal to 2 in eighty-three percent 83 (83%) of the patients.Polycystic ovarian syndrome has varying clinical manifestations, most commonly affecting the young women of reproductive age group. The commonest presenting complaint in the current study was menstrual abnormality. Majority of the patients had deranged hormonal profile which can lead to an increased risk of cardiovascular disease and type 2 DM. Thus, awareness regarding PCOS is important for early diagnosis and to prevent its sequalae to various complications.

Eating Disorders (ED) are associated with multiple physical complications that strongly affect the physical health of these young and fragile patients and can also cause significant mortality, the highest among psychiatric pathologies. Among the various organic complications, albeit still little known, the gynecological implications, up to infertility, are very widespread. Both among adolescent and adult patients, gynecological symptoms can be very widespread and range from menstrual irregularities to amenorrhea, from vaginitis to ovarian polycystosis, up to complications during the gestational phase and in postpartum, in addition to the possible consequences on the unborn child. Among the most frequent and significant gynecological disorders in women with ED, there are menstrual irregularities that may occur with oligomenorrhea or even amenorrhea. This symptom, although no longer part of the DSM-5 diagnostic criteria for defining Anorexia Nervosa (AN), must be considered a very relevant event in the overall evaluation of young women and adolescents with eating disorders. Functional Hypothalamic Amenorrhea in ED patients is related to psychological distress, excessive exercise, disordered eating, or a combination of these factors which results in suppression of the hypothalamic- pituitary-ovarian axis, resulting in hypoestrogenism. The objective of this paper is to summarize the causes and the mechanism underlying the menstrual disorders and to provide a better understanding of the correlation between the reproductive system and the mechanisms that regulate food intake and eating habits. In addition, early recognition of risk factors for eating disorders for gynecological implications can help put more accurate assessments of patients to prevent potentially fatal complications. The importance of the involvement of specialist gynecologists in the multidisciplinary team that has to follow patients with eating disorders is also discussed.

CapsuleOligo/amenorrhea is an independent risk factor of low ovarian response but not high ovarian response, particularly in women with low AMH levels.ObjectiveTo investigate the association of menstrual cycle length (MCL) with anti-Müllerian hormone (AMH) and ovarian response.MethodsThis was a retrospective cohort study. A total of 7471 women who underwent ovarian stimulation and oocyte retrieval were enrolled. The main outcome was the number of oocytes retrieved.Main ResultsA total of 5734 patients were eligible for analysis. In women without polycystic ovary syndrome (PCOS), serum AMH levels and antral follicle count were significantly lower in women with short cycles and higher in women with oligo/amenorrhea than those with a normal menstrual cycle. In women with PCOS, compared to women with a normal menstrual cycle, women with short cycles and women with oligo/amenorrhea showed higher antral follicle count and higher serum AMH levels. Compared with the 0-25th range group of AMH levels, 75-100th percentile groups showed a significantly increased rate of oligo/amenorrhea in women with and without PCOS [adjusted odds ratio (OR) =1.9 (1.04, 3.46), 2.4 (1.70, 3.35)]. In women without PCOS, the low ovarian response was more common in women with short cycles and less common in women with oligo/amenorrhea compared to women with normal cycles [OR=3.0 (2.38, 3.78), 0.7 (0.55, 0.96), respectively]. When adjusted for AMH levels, both short cycles and oligo/amenorrhea were associated with an increased risk of low response [adjusted OR=1.3 (1.02, 1.75), 1.3 (0.93, 1.86), respectively]. In women without PCOS and with low AMH levels, the low ovarian response was more common in women with short cycles as well as in women with oligo/amenorrhea [OR=1.5 (1.08, 1.98), 1.7 (1.08, 2.69), adjusted OR=1.2 (0.86, 1.74), 2.2 (1.31, 3.82), respectively].ConclusionAMH levels are significantly associated with increased risk of oligo/amenorrhea in women with and without PCOS. AMH is an indispensable confounder in the association between MCL and ovarian response in women without PCOS. Oligo/amenorrhea is an independent risk factor associated with a low ovarian response in women without PCOS, particularly those with low AMH levels.

Objective: To investigate the prevalence and the related characteristics of oligomenorrhea among women within childbearing age in China. Study design: A large-scale community-based investigation was conducted from 2013 to 2015. A total of 12,964 women aged 18–49 years from 9 provinces/municipalities in China were recruited for healthcare screening in local community health centers. Outcome measures include clinical history, ultrasonographic exam, and hormonal and metabolic parameters. Results: Among women within childbearing age in China, the prevalence of oligomenorrhea was 12.2% (1,579/12,964). Both sociodemographic factors and medical history were significantly associated with oligomenorrhea ( P Conclusions: Obesity, acne, seborrhea, acanthosis, larger ovarian size, and polycystic ovarian morphology were significantly associated with oligomenorrhea. The increase of anti-Mullerian hormone, total testosterone, and androstenedione level was also demonstrated in the oligomenorrhea group. Higher prevalence of infertility and medical treatment rate was observed in women with oligomenorrhea.

Objective To assess the safety of the levonorgestrel 52-mg intrauterine system (LNG-IUS) in women with a history of thrombosis or coagulopathy and to evaluate bleeding patterns. Methods A retrospective chart review was conducted of 117 women attending a clinic between 2007 and 2019. Their sociodemographic characteristics, hematologic status, reasons for using LNG-IUS, duration of use, use of oral anticoagulants, complications, and bleeding patterns were analyzed. Results Ninety-nine women had a history of thrombosis (71.7% in use of oral anticoagulants) and 18 had coagulopathies. No bleeding or any other complications occurred during placement of the LNG-IUS. Around two-thirds of the women reported amenorrhea or oligomenorrhea at 12, 24, and 54 months of follow-up, with no difference between the groups using the IUS for contraception or to treat heavy menstrual bleeding (HMB) (P=0.07), those with a history of thrombosis or coagulopathy (P=0.53), and users or non-users of oral anticoagulants (P=0.59). Conclusion The LNG-IUS is safe for women with hematologic disorders. It was associated with amenorrhea or oligomenorrhea in a large proportion of users up to 54 months of follow-up regardless of use of oral anticoagulants, reason for use of LNG-IUS (contraception or HMB), or history of coagulopathy or thrombosis.

Stress fractures are common among elite ballet dancers whereby musculoskeletal health may be affected by energy balance and overtraining.This study aimed to characterize bone health in relation to stress fracture history, body composition, eating disorder risk, and blood biomarkers in professional male and female ballet dancers.A single cohort of 112 dancers (male: 55, 25 ± 6 yr; female: 57, 24 ± 6 yr) was recruited. All participants underwent bone and body composition measures using dual-energy x-ray absorptiometry. In a subset of our cohort (male: 30, 24 ± 6 yr; female, 29, 23 ± 5 yr), a blood panel, disordered eating screen, menstrual history, and stress fracture history were also collected. Age-matched Z scores and young-adult T scores were calculated for bone mineral density (BMD) and body composition. Independent-samples t-tests and Fisher's exact tests were used to compare BMD, Z-scores, T scores, and those with and without history of stress fractures. A 1 × 3 ANOVA was used to compare BMD for those scoring 0-1, 2-6, and 7+ using the EAT26 questionnaire for eating disorder risk. Regression was used to predict BMD from demographic and body composition measures.Female dancers demonstrated reduced spinal (42nd percentile, 10%T-1) and pelvic (16th percentile, 76%T-1) BMD. Several anthropometric measures were predictive of BMD (P0.05, r = 0.65-0.81, standard error of estimate = 0.08-0.10 g·cm, percent error = 6.3-8.5). Those scoring1 on EAT26 had lower BMD than did those with a score of 0-1 (P0.05).Professional female ballet dancers exhibit reduced BMD, fat mass, and lean mass compared with the general population whereby low BMD and stress fractures tend to be more prevalent in those with a higher risk of disordered eating. Anthropometric and demographic measures are predictive of BMD in this population.

Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes.Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored.Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain.Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies. Methods: We analyzed data from 14 case–control studies including 16,594 women with invasive ovarian cancer (n = 13,719) or borderline ovarian disease (n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58–0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76–0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65–1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors (Pheterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors (Pheterogeneity < 0.0001). Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype. Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174–82. ©2017 AACR.

Eighty-four subjects, premenopausal female patients (n=42, mean (SD) age: 26.4 (4.2) years) diagnosed with polycystic ovary syndrome (PCOS) and age-matched healthy volunteers (n=42, mean (SD) age: 27.6(3.4) years), were included in this study. Data on physical examination, anthropometric measurements and blood biochemistry analysis were recorded for each subject along with analysis for SOCS1-1478 CA/del polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The relation of SOCS1-1478 CA/del polymorphism to PCOS status and insulin resistance was analysed via logistic regression analysis. Mean (SD) levels for BMI (28.5(6.5) vs.22.5 (4.9) kg/m(2), p

BackgroundPolycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. Previous studies have identified genetic variants associated with PCOS identified by different diagnostic criteria. The Rotterdam Criteria is the broadest and able to identify the most PCOS cases.ObjectivesTo identify novel associated genetic variants, we extracted PCOS cases and controls from the electronic health records (EHR) based on the Rotterdam Criteria and performed a genome-wide association study (GWAS).Study DesignWe developed a PCOS phenotyping algorithm based on the Rotterdam criteria and applied it to three EHR-linked biobanks to identify cases and controls for genetic study. In discovery phase, we performed individual GWAS using the Geisinger’s MyCode and the eMERGE cohorts, which were then meta-analyzed. We attempted validation of the significantly association loci (P−6) in the BioVU cohort. All association analyses used logistic regression, assuming an additive genetic model, and adjusted for principal components to control for population stratification. An inverse-variance fixed effect model was adopted for meta-analyses. Additionally, we examined the top variants to evaluate their associations with each criterion in the phenotyping algorithm. We used STRING to identify protein-protein interaction network.ResultsWe identified 2,995 PCOS cases and 53,599 controls in total (2,742cases and 51,438 controls from the discovery phase; 253 cases and 2,161 controls in the validation phase). GWAS identified one novel genome-wide significant variant rs17186366 (OR=1.37 [1.23,1.54], P=2.8×10−8) located nearSOD2. Additionally, two loci with suggestive association were also identified: rs113168128 (OR=1.72 [1.42,2.10], P=5.2 x10−8), an intronic variant ofERBB4that is independent from the previously published variants, and rs144248326 (OR=2.13 [1.52,2.86], P=8.45×10−7), a novel intronic variant inWWTR1. In the further association tests of the top 3 SNPs with each criterion in the PCOS algorithm, we found that rs17186366 was associated with polycystic and hyperandrogenism, while rs11316812 and rs144248326 were mainly associated with oligomenorrhea or infertility. Besides ERBB4, we also validated the association withDENND1A1.ConclusionThrough a discovery-validation GWAS on PCOS cases and controls identified from EHR using an algorithm based on Rotterdam criteria, we identified and validated a novel association with variants withinERBB4. We also identified novel associations nearbySOD2andWWTR1. These results suggest the eGFR and Hippo pathways in the disease etiology. With previously identified PCOS-associated lociYAP1, theERBB4-YAP1-WWTR1network implicates the epidermal growth factor receptor and the Hippo pathway in the multifactorial etiology of PCOS.

The mechanism underlying oligo/amenorrhea in exercising women is often presumed as hypothalamic inhibition secondary to energy deficiency; however, hyperandrogenism may provide an alternative mechanism in some exercising women. Our purpose was to compare reproductive, metabolic, and androgen profiles of exercising women with eumenorrheic, ovulatory menstrual cycles (n = 91), oligo/amenorrhea without evidence of hyperandrogenism (Oligo/Amen; n = 83), and oligo/amenorrhea with evidence of hyperandrogenism (Oligo/Amen-HA; n = 17), and determine the prevalence of oligo/amenorrhea with evidence of hyperandrogenism in exercising women. Self-reported menstrual history and quantification of daily estrogen and progesterone urinary metabolites determined reproductive status. Resting energy expenditure, body composition, and metabolic hormone concentrations determined metabolic status. Serum androgens and calculated free androgen index (FAI) determined androgen status. Groups were similar in age (22.4 ± 0.3 years), height (165.1 ± 0.5 cm), resting energy expenditure (1198.4 ± 12.0 kcal/day), and total triiodothyronine (85.0 ± 1.5 ng/dL) concentration. Oligo/Amen-HA had greater weight (60.0 ± 1.6, 56.1 ± 0.7 kg), body mass index (22.3 ± 0.4, 20.6 ± 0.2 kg/m2), percentage body fat (27.3% ± 1.4%, 24.4% ± 0.6%), fat mass (16.2 ± 1.0, 13.8 ± 0.4 kg), insulin (5.8 ± 0.7, 4.2 ± 0.3 μIU/mL), leptin (12.2 ± 2.3, 6.6 ± 0.7 ng/mL), FAI (6.1 ± 0.3, 1.7 ± 0.1), and luteinizing hormone/follicle-stimulating hormone (1.9 ± 0.3, 1.3 ± 0.2) compared with Oligo/Amen, respectively. In our sample, 17% of those with oligo/amenorrhea had concurrent hyperandrogenism. This study supports that oligo/amenorrhea in some exercising women is related to hyperandrogenism. Novelty Caution must be utilized when discriminating hypothalamic oligo/amenorrhea from hyperandrogenic oligo/amenorrhea. In our sample, 17% of those with presumed hypothalamic oligo/amenorrhea had concurrent hyperandrogenism. Exercise and/or mild energy deficiency may be protective against developing severe hyperandrogenic symptoms.

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.

Obesity has adverse effects on ovulation, menstrual cyclicity and oocyte development leading to clinical symptoms such as infertility and menstrual disorders. The Roux-en-Y gastric bypass (RYGB) leads to weight loss, improved insulin sensitivity and may improve ovarian function. In 31 premenopausal women, 18 eu- and 13 oligo-/amenorrhoic, we followed the changes in follicular phase sex hormones 3, 6 and 12 month after RYGB. The average weight loss during the first postoperative year was 39.6 kg. The insulin sensitivity and serum insulin improved markedly especially within the first three postoperative months. SHBG increased progressively and was doubled after 12 months. In contrast, total and free androgens and DHEA declined about 50% during the first three postoperative months and remained fairly constant hereafter. One year after surgery, 85% (11/13) of the women with oligo-/amenorrhea gained regular menstrual cycles. Our results indicate that some of the endocrine changes related to regulation of ovarian function occur very early after bariatric surgery.

Serum concentration of anti-Müllerian hormone (AMH) is a useful marker for ovarian reserve. Measurement of AMH in clinical practice has gained widespread use to predict parameters such as the ovarian response, menopause, and recovery after chemotherapy. However, undetectable AMH levels assayed by conventional enzyme-linked immunosorbent assay (ELISA) kits fail to predict depletion of follicles because of low sensitivity of the kits. We investigated whether a recently developed ultrasensitive ELISA kit, picoAMH, would be more effective at detecting very low AMH levels in association with menstrual status. We analyzed 68 women with undetectable serum AMH levels using an ELISA kit, AMH Gen II. The AMH concentration of the same samples was detected in 36 samples using picoAMH; 32 samples were within the standard range, and 4 samples were out of the standard range but still detectable. Thirty-two women whose AMH levels were undetectable using the picoAMH all showed amenorrhea. We also found a significant correlation between the classes of serum AMH levels (undetectable, detectable under the limit of quantification, and measurable within the assay range) and menstrual status. Five of the 6 amenorrheic women with detectable AMH eventually achieved follicle growth. The present study demonstrated that very low AMH levels detectable using picoAMH correspond well to current and future ovulation status. This suggests that serum AMH levels can be useful for the assessment of ovarian reserve and follow-up of women with a declined ovarian reserve.

Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carriers of CAH (33), respectively were selected. Forty-four females age-matched healthy controls were also enrolled and genotyped for CYP21A2. Clinical, hormonal and genetic data were collected. CYP21A2 monoallelic mutations, defining the heterozygous carriers state, were identified in subjects with clinical features including hirsutism, oligomenorrhoea, overweight and a PCO-like phenotype, particularly occurring in the age of adolescence. Consistently, levels of 17OHP and cortisol were found to be significantly different from NC-CAH. Overall, some clinical and laboratory findings including oligomenorrhea and 17OHP/cortisol ratio were observed as independent markers associated with carriers of CAH. Here we report a high prevalence of late-onset signs of polycystic ovary syndrome (PCOS) and hyperandrogenism in heterozygous carriers. The 17OHP/cortisol ratio may be a predictive tool to identify the carriers of CAH, even though specific cut-off values have not yet been identified.

Background. Acne is not only a skin condition but also a cardinal component of many systemic diseases or syndromes. This study was aimed to investigate the prevalence of acne in reproductive-age women in Sichuan province, China, and to evaluate acne as a skin problem alone or a symptom of gynecological/endocrinological disease. Methods. From October 2008 to September 2009, 1043 reproductive-age women from 19 to 45 years of age from seven communities of three districts in Sichuan province completed a standardized questionnaire and a physical examination. Acne was classified using the Pillsbury scale, and hirsutism was assessed using a modified Ferriman–Gallwey method. Diagnosis of polycystic ovary syndrome (PCOS) was based on the 2003 Rotterdam criteria. Some endocrine and metabolic markers were detected for the women diagnosed with PCOS related to acne and the control group. Results. The prevalence of acne was 32.5%, and the highest prevalence (9.6%) was seen in the 19–24-year-old age group. Prevalence among women eating dessert frequently, exercising seldom, or among sedentary workers was significantly higher in the acne group (14.1%, 55.6%, and 51.3%, respectively) than in the nonacne group (10.8%, 45.7%, and 35.5%; all P Conclusion. When reproductive-age women with acne are encountered in gynecology–endocrinology or dermatology clinics, physicians should consider evaluating them from PCOS, hyperandrogenism, or acne alone.

The aim of this study was to evaluate the efficacy of the herbal tea based on Foeniculum vulgare, on inducing regular bleeding in women with oligomenorrhea and secondary amenorrhea( oligo/amenorrhea).Forty women aged 18- 40 with oligo/amenorrhea were enrolled in this randomized controlled clinical trial and were allocated to two groups equally. The women in the first group were treated by Fomentex (Foeniculum vulgare / Mentha longifolia / Vitex agnus-castus) herbal tea 11.2 g/day in 2 divided doses for 2 weeks and the second group were treated by medroxy progesterone acetate (MP)10 mg/day for the last 10 days of their menstrual cycles. The intervention was repeated in three cycles of menstruation in both groups. Bleeding pattern was documented by the patient on diary cards. The occurrence (yes/no) of bleeding, the regularity of bleeding pattern, the interval of cycles, the duration of bleeding, the volume of blood flow, the hormonal parameters (total testosterone, free testosterone luteinizing hormone and follicle-stimulating hormone), and the endometrial thickness in sonography before and after the intervention were evaluated and compared as outcomes.The number of women with bleeding during the first cycle was in the Fomentex group and the MP group 83.3% and 94.1% respectively (p = 0.61). The regularity of bleeding did not significantly differ in patients treated with Fomentex from those given MP (66.7% vs. 94.1%; p = 0.088). Mean interval of cycles decreased in both groups after intervention (P0.001). Mean duration decreased significantly in MP group after the intervention but it was not different in patients treated with Fomentex. The difference between 2 groups was not significant (P=0.705). Volume of blood flow, with regard to Pictorial Blood Assessment Chart (PBAC), increased significantly in MP group after the intervention (P=0.001) and it was not different in patients treated with Fomentex (P=0.757); however, difference between 2 groups was not significant (P=0.063). The percentage of patients with on time menstruation in the next (drug-free) episode, was higher in the Fomentex group compared with the MP group (50% vs. 23.5%; p = 0.105). Secondary outcomes such as dysmenorrhea, acne and hirsutism reduced in the Fomentex group (P≤0.05), while they increased in the MP group (P=0.007). At the end of the treatment, there was a significant decrease in luteinizing hormone, total testosterone and free testosterone in patients taking Fomentex. The decrease of endometrial thickness, was significant in both groups after the intervention (P=0.001), but the difference between 2 groups was not significant (P=0.58). No notable complication or side effect was reported in relation to Fomentex.Fomentex herbal tea is a safe, well-tolerated, and effective choice in inducing bleeding and maintaining regular bleeding in women with oligo/amenorrhea.

Vitamin D (VD) plays a crucial role in calcium metabolism as well as immunological and endocrine homeostasis. Previous studies revealed strong inverse correlation between VD levels and insulin resistance, parathyroid dysfunctions and autoimmune thyroid disease. Insufficient evidence concerns its dependency of ovarian hormones. Malfunctioning of the ovaries results in menstrual disorders that are one of the most common endocrine impairments in young women of reproductive age.The study was aimed to evaluate the correlation between 25(OH)D serum concentration and estradiol, testosterone as well as body mass index (BMI) in women with oligomenorrhea. 134 women of reproductive age with oligomenorrhea were eligible for the study. 25-hydroxyvitamin D [25(OH)D], estradiol, testosterone and sex hormone-binding globulin (SHBG) were measured using chemiluminescence immunoassay. Free androgen index (FAI) and body mass index (BMI) were calculated.Critical 25(OH)D deficiency (10 ng/ml) was found in 13.4% of women, the risk of deficiency (30 mg/dl) was diagnosed in 69.4%, while sufficient level of VD (30 mg/ml) in 17.2% of them. Significant negative correlation was detected between 25(OH)D and estradiol serum concentrations (r=-0.2; p=0.049), as well as BMI levels (r=-0.22; p=0.01). However, no significant correlation was found between 25(OH)D and testosterone (r=-017; p=0.055), SHBG (r=0.08; p=0.4) and FAI (r=-0.1; p=0.24).Thorough assessment of vitamin D deficiency/insufficiency is required among patients with menstrual disorders, especially those overweighed and obese. Early screening and VD supplementation in women with estrogen-dependent disorders may become a part of routine management in order to optimize endocrine health.

Amenorrhea is important for women’s bone health. However, few have reported reproductive, anthropometric (body mass index [BMI], height) and bone health (areal bone mineral density [BMD], prevalent fractures) in a population-based study. The purposes of this cross-sectional study of women in the randomly-selected Canadian Multicentre Osteoporosis Study (CaMos) population were: (1) to describe reproductive, demographic, anthropometric and lifestyle variables; and (2) in menstruating women, to relate reproductive and other variables to BMD at the lumbar spine (L1-4, LS), femoral neck (FN) and total hip (TH) sites and to prevalent fragility fractures. This study describes the reproductive characteristics of 1532 women aged 30–60 years. BMD relationships with reproductive and other variables were described in the 499 menstruating women. Mean menarche age was 12.8 years, 96% of women were parous and 95% had used combined hormonal contraceptives (CHC). Infertility was reported by 9%, androgen excess by 13%, amenorrhea by 8% and nulliparity by 4%. LS BMD was negatively associated with amenorrhea and androgen excess and positively related to current BMI and height. A later age at menarche negatively related to FN BMD. BMI and height were strongly related to BMD at all sites. Prevalent fragility fractures were significantly associated with quartiles of both LS and TH BMD.

To compare pregnancy rates following ovulation induction in anovulatory women with clomiphene citrate vs. letrozole and to determine the relative confounding effect of inducing menses or not. The study also evaluated whether starting these anti-estrogen drugs later in the menstrual cycle has-less adverse effect on endometrial thickness.Prospective series with choice by physician of inducing menses or not or choosing clomiphene citrate or letrozole for ovulation induction. Peak endometrial thickness was compared between drugs and between those conceiving or not.There were 21 first cycles using letrozole and 42 using clomiphene. Menses were not induced in 18/21 (86%) letrozole cycles and 24/42 (57%) clomiphene cycles. Clinical pregnancies occurred in four (22.2%) letrozole cycles without induced menses with one miscarriage vs. 4/24 (16.6%) clomiphene cycles, no mis- carriage. One of three (33.3%) letrozole cycles with menses induced achieved a clinical pregnancy vs. only 1/18 (5.5%) of clomiphene cycles. There were no miscarriages.Though the endometrial thickness was higher with clomiphene without induced menses vs. menses induced (11 mm vs. 9.5 mm), one cannot explain the trend for lower pregnancy rates in women with induced menses because of thinner endometria since the thickness was 10.3 mm for clomiphene and 10.0 with letrozole.

Objectives: To investigate the effect of metformin on endometrial receptivity in women with polycystic ovary syndrome (PCOS). Methods: Twenty volunteer women with polycystic ovaries and oligomenorrhea were prospectively investigated. All women were treated with exogenous estradiol and progesterone to simulate a normal menstrual cycle (28-day duration) after GnRH-induced pituitary desensitization. Ten of the women received no other medication (group A, control), while the remaining 10 received metformin (group B, metformin). Endometrial biopsy was performed in all women on day 21 of the 2 simulated cycles. Results: The expression of corticotropin – releasing hormone and urocortin in the endometrium was investigated. There was no significant difference between the 2 groups. A 3-day delay in the secretory maturation of the glandular epithelium relatively to the stroma was observed in 7 out of 10 women of group B (70%) as compared to only 1 out of 10 women of group A (10%, p = 0.02). Conclusions: It is shown for the first time that metformin administration to women with PCOS did not affect the expression of endometrial receptivity markers but delayed histological glandular maturation. It is suggested that metformin may have an impact on the function of the endometrium in PCOS.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia.

The aim of this study was to evaluate and compare the effects of spironolactone and spironolactone plus metformin treatments on body mass index (BMI), hirsutism score, hormone levels, and insulin resistance in women with polycystic ovary syndrome (PCOS). Thirty-seven patients with PCOS were randomly assigned to receive spironolactone 100 mg/d (spironolactone group, 18 patients) or spironolactone 100 mg/d plus metformin 2000 mg/d (combination group, 19 patients) for 12 months. BMI, modified Ferriman-Gallway score (FGS), serum levels of regarding hormones, and homeostasis model assessment of insulin resistance (HOMA-IR) index were assessed before and after the treatments. Six patients in the spironolactone group and four patients in the combination group reported inter-menstrual vaginal bleeding during treatments. In hirsutism scores, the spironolactone therapy resulted in 25.2% reduction, while combination therapy resulted in 28.3% reduction (p > 0.05, between groups). When the groups were compared in terms of percent changes in BMI, FGS, HOMA-IR, and hormone values other than free testosterone, no significant difference was noted. In the present study, FGSs were significantly decreased in both groups; however, combination therapy was not more effective than spironolactone alone in terms of BMI, FGS, hormone levels, or insulin resistance.

Objective Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. Study design A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A – patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B – patients with H plus O (without PCO); C – patients with H plus PCO (ovulatory phenotype); D – patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. Results Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59–13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40–211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01–0.51). Conclusions The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group.

Most clinicians are not prepared to provide integrated personal care to address all the clinical needs of women with primary ovarian insufficiency. Design thinking is an engineering methodology used to develop and evaluate novel concepts for systems operation. Here we articulate the need for a seamlessly integrated mobile health system to support genomic research as well as patient care. We also review the pathophysiology and management of primary ovarian insufficiency. Molecular understanding regarding the pathogenesis is essential to developing strategies for prevention, earlier diagnosis, and appropriate management of the disorder. The syndrome is a chronic disorder characterized by oligo/amenorrhea and hypergonadotropic hypogonadism before age 40 years. There may be significant morbidity due to: 1) depression and anxiety related to the loss of reproductive hormones and infertility; 2) associated autoimmune adrenal insufficiency or hypothyroidism; and 3) reduced bone mineral density and increased risk of cardiovascular disease related to estrogen deficiency. Approximately 5% to 10% of women with primary ovarian insufficiency conceive and have a child. Women who develop primary ovarian insufficiency related to a premutation in FMR1 are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability. In most cases of spontaneous primary ovarian insufficiency no environmental exposure or genetic mechanism can be identified. As a rare disease, the diagnosis of primary ovarian insufficiency presents special challenges. Connecting patients and community health providers in real time with investigators who have the requisite knowledge and expertise would help solve this dilemma.

Objective Menstrual irregularity is one of the major complaints in women of reproductive age. The aim of this study was to evaluate the complications in women with different menstrual disturbances. Materials and methods This is a retrospective study. A total of 576 women were screened first, and 470 women were included later [257 women with oligo/amenorrhea (149 hyperandrogenic and 108 nonhyperandrogenic women) and 213 normocyclic controls]. Endocrine and metabolic parameters and insulin resistance were compared among different menstrual patterns. Results The average duration of menstrual cycle length was positively correlated with age, levels of androgens and prolactin, lipid profiles, and the parameters of insulin resistance. Hyperandrogenic women with amenorrhea had higher levels of androgens and more lipid profiles disorders than hyperandrogenic women with oligomenorrhea. However, nonhyperandrogenic women with amenorrhea had a degree of insulin resistance and metabolic disturbance similar to that of nonhyperandrogenic women with oligomenorrhea. Interestingly, for women with normal prolactin levels, serum prolactin levels were significantly lower in amenorrhea than oligomenorrhea in both hyperandrogenic and nonhyperandrogenic groups. Conclusion The degree of menstrual disturbances does not correlate with the severity of insulin resistance and metabolic disturbances in women without excess levels of androgen. For women with normal prolactin levels, amenorrheic patients had significantly lower serum prolactin levels than oligomenorrheic patients.

Aims: To present a study on severe Asherman's syndrome after open myomectomy and investigate the possible reasons for this outcome. Methods: This study involves a rare case of a 38-year-old nulliparous woman who underwent a relatively minor and straightforward open myomectomy in a university hospital setting, during which the uterine cavity was not entered and there were no post-operative complications. Post-operatively the patient had oligomenorrhoea for over a year. The patient was investigated with three-dimensional power Doppler angiography of the uterus and underwent diagnostic/operative hysteroscopy. Main outcome measures were to sonographically assess the blood flow and vascularisation throughout the uterus and to hysteroscopically confirm diagnosis of Asherman's syndrome and treat the patient at the same time. Results: Sonographically there was reduced perfusion in the outer part of the uterus and the scarred areas of the endometrium. Upon hysteroscopic confirmation of diagnosis, the division of adhesions led to a normal sized uterine cavity. Conclusions: Among the predisposing and causal factors that have been implicated in post-operative adhesion formation, endometrial trauma, infection and tissue hypoxia are considered the most important. This case supports a role for tissue hypoxia in the development of Asherman's syndrome after open myomectomy.

SummaryObjective Although menstrual irregularity is associated with insulin resistance and hyperandrogenism, the relationship between the severity of menstrual infrequency and clinical phenotypes in young women with oligomenorrhoea (OM) is unclear. We evaluated whether a longer menstrual cycle length is associated with less favourable metabolic features. Design/Patients/Measurements A total of 1174 young women (aged 19–39 years) with a menstrual cycle length over 40 days and 1430 women with regular menstrual cycles participated voluntarily. Metabolic parameters, insulin sensitivity index (ISI) and testosterone were measured. Oligomenorrhoeic women were divided into three groups: (i) polycystic ovary syndrome (PCOS) by National Institute of Health criteria, (ii) severe OM (menstrual cycle length >60 days), and (iii) mild OM (menstrual cycle length 40–60 days). Results In normal-weight women (BMI

Context: Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. Objectives: To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Design: Population-based follow-up. Setting: Northern Finland Birth Cohort 1966 with 15-year follow-up. Participants: At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Interventions: Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Main Outcomes: Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Results: Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Conclusions: Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression., We studied psychological distress in women with PCOS symptoms and found high anxiety and depression rates in women with PCOS or isolated hirsutism lasting until perimenopausal age.

Objective There is scarcity of information on the prevalence of female genital tuberculosis (FGTB) in the community. The present study was carried out to estimate the prevalence of FGTB, its risk factors and associated clinical features. Study design Community-based cross-sectional survey. Methods This study was carried during October 2011 and May 2014 in the Andaman Islands. A total of 13,300 women aged 20–59 years were primarily screened using a structured questionnaire. About 721 (5.4%) were found initially eligible for screening for genital tuberculosis by clinical examination and specimen collection for laboratory tests but only 460 (63.8%) expressed their willingness. Endometrial specimens were collected from 405 (88%) subjects. The association of the potential risk factors with genital tuberculosis was tested by Chi-squared test. A similar analysis was performed to identify clinical features associated with genital tuberculosis. Results The estimated prevalence of FGTB was 45.1 cases per 100,000 women (95% confidence interval [CI]: 16.6–98.1). Infertility and oligomenorrhoea were identified as clinical features associated with FGTB. Past history of tuberculosis and history of close contact with tuberculosis cases were identified as risk factors. Conclusions This study shows the prevalence of FGTB among the female population of the Andaman Islands. Though the estimated prevalence was close to the expected prevalence, but as only 63.8% of the eligible women could be adequately screened, a much higher prevalence of FGTB could not be ruled out. Infertility, oligomenorrhoea, past history of tuberculosis and contact with tuberculosis case were identified as factors associated with genital tuberculosis.

OBJECTIVE: To study the association between body size from birth to adulthood and self-reported symptoms of polycystic ovary syndrome (PCOS), particularly hirsutism and menstrual disturbances. DESIGN: Longitudinal, population-based study of a cohort of women born in 1966 in northern Finland. The study population included 2007 women who were not pregnant and did not use hormonal contraception. Of these 528 (26%) had self-reported symptoms of PCOS. RESULTS: Weight at birth, gestational age, being small for gestational age or growth retardation at birth were not associated with PCOS symptoms at 31 y. An increased risk of PCOS symptoms was observed among women with abdominal obesity (waist/hip ratio >85th percentile) at 31 y who had normal weight in adolescence and were overweight (body mass index (BMI) 25.0-29.9 kg/m(2)) or obese (BMI>30.0 kg/m(2)) at 31 y (relative risk (RR) (95% CI) 1.44(1.10-1.89)), and among women with abdominal obesity who were overweight or obese at both 14 and 31 y (1.71 (1.30-2.24)). A total of 30% and 41% of the women with PCOS symptoms in these groups could be attributed, respectively, to overweight, obesity and abdominal obesity at 31 y. CONCLUSIONS: These results suggest that obesity in adolescence and in adulthood, and also weight gain after adolescence, particularly in the presence of abdominal obesity, are associated with self-reported PCOS symptoms in adulthood. Thus, based on the results from intervention studies treating PCOS and the results of this study, the prevention of obesity and abdominal obesity is important among young women.

Summary Objective Application of the newly introduced Rotterdam criteria for polycystic ovary syndrome (PCOS) generates four phenotypic subgroups, defined by the presence/absence of three diagnostic elements: polycystic ovarian (PCO) morphology (P); hyperandrogenism (H); and oligo-amenorrhoea (O). Whilst PCOS is associated with adverse metabolic features, the strength of the association within individual subgroups is not established. We characterized the metabolic and endocrine profiles of PCOS women who are oligomenorrhoeic but normoandrogenaemic, and compared these to other PCOS women and controls. Design Retrospective dataset analyses. Patients A total of 309 Europid PCOS women, all with PCO morphology, of whom 191 were also hyperandrogenaemic and oligomenorrhoeic (PHO), 76 hyperandrogenaemic with normal menses (PH) and 42 oligomenorrhoeic but normoandrogenaemic (PO); plus 76 Europid control women without PCOS. Measurements Metabolic parameters: fasting insulin, lipids, homeostasis model assessment (HOMA) measures of insulin sensitivity; endocrine variables: LH, FSH; prevalence of metabolic syndrome. Results Insulin sensitivity: PO women were indistinguishable from controls, and markedly less insulin-resistant than PHO women ( vs. controls, P = 0·38 after adjustment for BMI and age; vs. PHO, P = 0·003). Metabolic syndrome: the prevalence in PO women (7·1%) was similar to that in controls (3·9%), and lower than in PHO women (29·3%, P < 0·0001). LH levels: PO women were intermediate between controls ( vs. controls, P = 0·008) and PHO women ( vs. PHO, P = 0·06). Conclusions Normoandrogenaemic, oligomenorrhoeic women with PCOS are metabolically similar to control women with significantly fewer metabolic features than PCOS women who are also hyperandrogenaemic. However, higher than normal LH and lower sex hormone-binding globulin (SHBG) concentrations in the PO women support the view that they form part of the spectrum of PCOS.

OBJECTIVE: To investigate the occurrence of oligo-amenorrhoea and hirsutism, infertility and metabolic morbidity among first-degree relatives of women with and without self-reported oligo-amenorrhoea and hirsutism. DESIGN: Nested case-control study. SETTING, POPULATION AND METHODS: A postal questionnaire about symptoms of oligo-amenorrhoea and hirsutism was sent to all women of the Northern Finland Birth Cohort 1966 (n = 5889). From this population were randomly selected 98 women with both symptoms and 163 without symptoms. A further questionnaire on the occurrence of oligo-amenorrhoea, hirsutism, infertility, early balding and metabolic morbidity in their relatives was sent to this subpopulation. MAIN FINDINGS: We obtained data on 183 relatives of 43 women with symptoms and 412 relatives of 86 symptomless women. Compared with relatives of symptomless women, mothers of women with symptoms suffered significantly more often from hirsutism and menstrual disorders, and sisters more often from hirsutism and infertility, and had fewer children and were more often childless. There was an increased prevalence of diabetes in the sisters and of hypertension in the fathers of women with symptoms. CONCLUSIONS: These results strengthen earlier findings of significantly increased metabolic and reproductive morbidity in the relatives of women with symptoms of PCOS.

A 35-year-old house wife attended our clinic with oligomenorrhea for the last three months. She also complained of diffuse body ache, joint pain and decreased bowel movements. Very often she experienced choking sensation in the throat and had difficulty in swallowing solid food. On examination, goitre was absent but a globular pink colour mass was detected at the base of the tongue.

Purpose: Calcitonin gene-related peptide (CGRP) is an amino acid neuropeptide with widespread expression. It has potent effects on lipid and energy metabolism. It induces insulin resistance. This study was planned to determine CGRP levels in women with polycystic ovary syndrome (PCOS). Methods: Forty-seven women with PCOS and 34 healthy controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, postprandial and fasting glucose, insulin and other hormones (gonadotropins, androgens) and CGRP levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Results: Waist measurements, postprandial and fasting glucose and fasting insulin levels and free androgen index and HOMA-IR were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower high-density lipoprotein cholesterol levels than healthy subjects. Serum CGRP levels were higher in study subjects than in controls, although it was statistically insignificant. Conclusions: Serum CGRP level was not related with insulin resistance, ovarian hyperandrogenism and dyslipidemia in abdominally obese women with PCOS. These outcomes propose that CGRP may not play a pivotal role in the pathogenesis of PCOS. © 2012 Springer-Verlag Berlin Heidelberg.

WOS: 000308511500012 PubMed: 22534402 Objective: The relationship between menstruation disorders and antidepressant drugs usage in women remains unclear. In this study, we aimed to investigate the incidence rate of antidepressant-related menstruation disorders and to examine whether or not antidepressant use is associated with menstrual disorders in women. Methods: The study sample was gathered from three centers and four hospitals. A total of 1432 women who met the criteria of inclusion were included in the study. The sample was divided into two groups: the antidepressant group (n=793) and the control group (n=639). The menstruation disorders were established with reports from the study participants on the basis of related gynecological descriptions. Results: The prevalence of menstrual disorders was significantly higher in the antidepressant group (24.6%) than the control group (12.2%). The incidence of antidepressant-induced menstruation disorder was 14.5%. The antidepressants most associated with menstrual disorders were paroxetine, venlafaxine, sertraline and their combination with mirtazapine. Overall, the incidence rate was similar in women receiving selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors. Conclusions: The results of the present study suggest that menstruation disorders are frequently observed in women taking antidepressants and that it appears to be associated with antidepressant use at least in some women. (C) 2012 Elsevier Inc. All rights reserved.

Young reproductive-age women with irregular menses and androgen excess are at high risk for unfavorable metabolic profile; however, recent data suggest that menstrual regularity and hyperandrogenism improve with aging in affected women approaching menopause.The objective of the study was to determine whether women with hyperandrogenemia (HA) and a history of oligomenorrhea (Oligo) are at an elevated risk for metabolic syndrome (MetS) at the early stages of menopausal transition.Baseline data from 2543 participants (mean age of 45.8 yr) in the Study of Women's Health Across the Nation were analyzed. Women with a lifetime history of more than one 3-month interval of nongestational and nonlactational amenorrhea were classified as having a history of Oligo. The highest tertile of serum testosterone was used to define HA. Women with normal serum androgens and eumenorrhea were used as the reference group. Logistic regression models generated adjusted odds ratios (AOR), controlling for age, ethnicity, body mass index, smoking, and study site.Oligo was associated with MetS only when coincident with HA [AOR of 1.93 for Oligo and HA [95% confidence interval (CI) 1.17-3.17], AOR of 1.25 for Oligo and normal androgens (95% CI 0.81-1.93)]. In contrast, HA conferred a consistently significant risk for MetS, regardless of the menstrual frequency status [AOR of 1.48 for HA and eumenorrhea (95% CI 1.15-1.90)].Our results suggest that HA but not history of Oligo is independently associated with the risk of prevalent MetS in pre- and perimenopausal women in their 40s.

We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to

Background: It is hypothesized that exercise can lead to a decrease in breast cancer risk through several hormonal and nonhormonal mechanisms. The WISER (Women In Steady Exercise Research) study investigated the effects of aerobic exercise on premenopausal sex hormone levels. Methods: Three hundred ninety-one sedentary, healthy, young eumenorrheic women were randomized either into an exercise intervention of 30 minutes of aerobic exercise 5 times a week for approximately 16 weeks (n = 212) or into a control group (n = 179). Serum levels of estradiol, estrone sulfate, testosterone, and sex hormone–binding globulin (SHBG), all in the midfollicular phase, and of progesterone, in the midluteal phase, were measured at baseline and at the end of the 16-week period. Results: Compared with the controls (n = 153), exercisers (n = 166) experienced significant increases in aerobic fitness, lean body mass, and decreases in percent body fat. There were no significant changes in body weight and menstrual cycle length between or within groups. Progesterone decreased significantly in exercisers; however, this reduction was similar to that of the control group. No significant changes between or within groups were found for any of the other sex hormones or SHBG. Conclusions: In premenopausal women, 16 weeks of 150 minutes per week of moderate aerobic exercise in young women did not significantly alter sex hormone or SHBG levels. Impact: Any favorable effects that moderate aerobic exercise without an associated weight change may have on breast cancer risk in premenopausal women are unlikely to be a consequence of changes in levels of sex hormones or SHBG. Cancer Epidemiol Biomarkers Prev; 20(6); 1098–106. ©2011 AACR.