Reproductive functions and pregnancy outcome in female patients with celiac disease.

BACKGROUND AND AIM: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD. METHODS: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited. RESULTS: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001]). CONCLUSIONS: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD.

Nightshift work and irregular menstrual cycle: 8-year follow-up cohort study.

BACKGROUND: Irregular menstruation is a major health problem among women, although its association with nightshift work remains controversial. AIMS: To study the association between nightshift work and irregular menstrual cycle among female workers and investigate any differences according to sleep quality, working hours or obesity. METHODS: This study included female workers who underwent health examinations from 2012 to 2019. Nightshift work, working hours, sleep quality and menstrual cycles were assessed using self-administered questionnaires. Irregular menstrual cycle was defined as self-reported irregular or ≥36 days. Adjusted odds ratios and 95% confidence intervals (CIs) were calculated by multivariable logistic regression; adjusted hazard ratios (95% CIs) for incident irregular menstrual cycle were calculated by Cox proportional hazard models with time-dependent analysis. RESULTS: The study participants were 87 147 in the cross-sectional study and 41 516 in the longitudinal study. After adjusting for all covariates in the cross-sectional analyses, the odds ratio for prevalent irregular menstrual cycle among female nightshift workers versus the reference was 1.26 (95% CI 1.2-1.33). In the cohort study, the adjusted hazard ratio for incident irregular menstrual cycle among nightshift workers was 1.95 (95% CI 1.61-2.35) in the period after 6 years. No significant differences were observed among subgroups stratified by sleep quality, working hours or obesity. CONCLUSIONS: Nightshift work is associated with an increased risk of both prevalent and incident irregular menstrual cycle in female workers without significant interactions by sleep quality, working hours or obesity.

Contemporary Issue: Health and Safety of Female Wrestlers.

ABSTRACT: Female wrestling has grown exponentially over the past decade. Within the United States, 46 states now recognize female high school wrestling, and 153 colleges have programs. It is on track to become an NCAA championship-level sport in 2026. A primary health and safety risk among this cohort pertains to rapid weight loss strategies. These can lead to intentional caloric restriction and decreased body fatness, with the perceived goal of attaining a competitive advantage. Low energy availability and low body fatness are associated with a number of health concerns including menstrual dysfunction and loss of bone mineral density in girls and women. The current recommendation of 12% as a minimum for percentage body fat is very likely too low, opening the door for health perturbations among this population. The minimum threshold might more appropriately fall within the range of 18% to 20%. Body fat assessment methods, primarily skinfold measures that are used to guide weight class selection, have not been adequately validated among this population and therefore should be an area of research focus, while also exploring alternative assessment techniques. Further, we recommend that weight cycling, restrictive energy intake, and intentional dehydration be avoided. Research should assess the effects of frequent weight cycling (to "make weight") and prolonged periods of low body fat on the reproductive and bone health of these athletes. Finally, research and clinical evaluations on female wrestlers are limited, and we offer a list of research priorities for future investigation into this contemporary issue.

Menstrual abnormalities after COVID-19 vaccination in the Netherlands: A description of spontaneous and longitudinal patient-reported data.

AIMS: During the COVID-19 vaccination campaigns, the number of reports of menstrual abnormalities increased rapidly. Here, we describe the nature and potential risk factors associated with menstrual abnormalities based on spontaneously reporting data as well as data from a prospective cohort event monitoring (CEM) study as these are poorly studied. METHODS: Reports of menstrual abnormalities received by the Netherlands Pharmacovigilance Centre Lareb in the spontaneous reporting system between February 2021 and April 2022 were summarized. In addition, logistic regression analysis was performed on the reported menstrual abnormalities in the CEM study to assess the association between person characteristics, prior SARS-CoV-2 infection and use of hormonal contraceptives and the occurrence of menstrual abnormalities after vaccination. RESULTS: We analysed over 24 000 spontaneous reports of menstrual abnormalities and over 500 episodes (among 16 929 included women) of menstrual abnormalities in the CEM study. The CEM study showed an incidence of 41.4 per 1000 women aged ≤54 years. Amenorrhoea/oligomenorrhoea and heavy menstrual bleeding collectively accounted for about half of all abnormalities reported. Significant associations were observed for the age group 25-34 years (odds ratio 2.18; 95% confidence interval 1.45-3.41) and the Pfizer vaccine (odds ratio 3.04; 95% confidence interval 2.36-3.93). No association was observed for body mass index and presence of most comorbidities assessed. CONCLUSION: The cohort study showed a high incidence of menstrual disorders among women aged ≤54 years, and this observation was supported by the analysis of spontaneous reports. This suggests that a relation between COVID-19 vaccination and menstrual abnormalities is plausible and should be further investigated.

Practical considerations for diagnosis and treatment of polycystic ovary syndrome in adolescence - distilling guidelines into clinical practice.

PURPOSE OF REVIEW: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adults may overdiagnose PCOS in adolescents. Since 2015, three guidelines have developed adolescent-specific diagnostic criteria and treatment recommendations. In this review, we compare and contrast the recommendations to assist in the practical application to clinical practice. RECENT FINDINGS: The guidelines agree that hyperandrogenism with menstrual irregularity be diagnostic criteria for PCOS in adolescents yet have slight differences in how to diagnose hyperandrogenism and in the definition of menstrual irregularity. The diagnostic option of 'at risk for PCOS' is recommended for those girls presenting with criteria within 3 years of menarche or with hyperandrogenism without menstrual irregularity, with re-assessment later in adolescence. Lifestyle changes is first line treatment. Treatment with combined oral contraceptives or metformin is suggested, using patient characteristics and preferences to guide decision-making. SUMMARY: PCOS is associated with long term reproductive and metabolic complications and will present during adolescence. Yet, diagnostic features may overlap with normal adolescent physiology. The recent guidelines strove to develop criteria to accurately identify girls with PCOS allowing early surveillance and treatment yet avoid overdiagnosis of normal adolescents.

MENSTRUAL DISORDER IN ADOLESCENTS DURING WAR.

OBJECTIVE: The aim: To investigate the peculiarities of menstrual cycle disorders in teenagers against the background of excessive stress in order to develop a scientifically based set of measures for their correction. PATIENTS AND METHODS: Materials and methods: 120 girls aged 9-18 who were in the war zone or became forced migrants were examined. Examination methods included anamnesis collection, assessment of psycho-emotional state, anthropometry, laboratory and instrumental studies. RESULTS: Results: It was found that the frequency of menstrual cycle disorders in the subjects was 65.8% (n = 79). Among menstrual cycle disorders: dysmenorrhea - 45.6% (n = 36), excessive menstruation - 27.8% (n = 22), secondary amenorrhea - 26.6% (n = 21). 71.7% (n = 86) of the examinees noted a change in eating behavior over the past few months. Almost half of these children had dyshormonal disorders or met the criteria of metabolic syndrome - 45.3% (n = 39). CONCLUSION: Conclusion: Timely detection and adequate correction of psycho-emotional and metabolic disorders in adolescent girls in stressful conditions contributes to the prevention of disorders of menstrual and reproductive function.

CLINICAL PROFILES AND CHARACTERISTICS OF MENSTRUAL DYSFUNCTION IN WOMEN AFTER SUFFERING FROM COVID-19 OR VACCINATION.

OBJECTIVE: The aim: To investigate changes in the characteristics of menstrual function in women after suffering from Covid-19 or vaccination against SARS-CoV-2. PATIENTS AND METHODS: Materials and methods: After the retrospective analysis of 378 medical records patients were divided into: Group 1 (177 women) with menstrual function disorders (MFD) after COVID-19, Group 2 (121 women) with MFD after SARS-CoV-2 vaccination, Group C (80 women) without MFD after COVID-19 or vaccination (controls). The study focused on the clinical and hormonal menstrual cycle characteristics and factors influencing MFD. RESULTS: Results: Dyshormonal thyroid disorders were observed in 63.0% of Group 1 and 45.7% of Group 2 patients; hyperprolactinemia - in 31.0% and 39.4%, hyper¬estrogenia - in 50% and 21%, and hyperandrogenism - in 39% and 20%. MFD was associated with hyperandrogenism with concurrent hyperprolactinemia, in the context of thyroid dysfunction; and with changes of gonadotropin production, along with normal and elevated estrogen concentrations and worsening of mental health that suggest disruption of central regulatory and feedback mechanisms in the pituitary-thyroid-ovarian system under the stressors influence. CONCLUSION: Conclusions: There are changes in the menstrual cycle associated with disruption of the hypothalamus-pituitary-ovary system and thyroid function in women after suffering from Covid-19 or vaccination. To reestablish reproductive homeostasis, employing a personalized diagnostic strategy is recommended, encompassing the evaluation of thyroid gland status, hormonal profiling, and the consideration of psychosocial facets.

Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation.

As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.

Hyperandrogenism and menstrual imbalance are the best predictors of metformin response in PCOS patients.

BACKGROUND: Moving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks). METHODS: One hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients' baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk. RESULTS: At 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation. CONCLUSIONS: In women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin response. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.

Factors associated with regularity and length of menstrual cycle: Korea Nurses' Health Study.

BACKGROUND: Menstrual cycle characteristics are linked to reproductive function and long-term health outcomes. This study aimed to evaluate menstrual cycle patterns, characterized by regularity and length, and associated factors among women in the Korea Nurses' Health Study. METHODS: A total of 9335 premenopausal women aged 22-45 years were included in this cross-sectional study. Regularity and length of menstrual cycles were self-reported, and their associations with reproductive, lifestyle, and occupational factors were examined using binomial and multinomial logistic regression models. Adjusted least-square means of menstrual distress, depressive symptoms, stress, fatigue, anxiety, and sleep problems were estimated according to menstrual cycle characteristics using generalized linear models. RESULTS: Twenty-one percent of nurses reported having irregular menstrual cycles (variability > 7 days). Ten percent, 64%, and 26% had menstrual cycle length of < 26, 26-31, and 32-50 days, respectively. Variability and length of cycles decreased with age and increased with age at menarche. Parous women showed low tendency of irregular cycles. Women with body mass index (BMI) > 25 kg/m2 had higher odds of irregular (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.40-2.03) and long cycles (OR 1.31; 95% CI 1.08-1.58) than those with BMI 18.5- < 23 kg/m2. Irregular cycles were less common in women performing vigorous physical activity, but more common in those with prolonged standing or frequent heavy lifting at work. Frequent rotating night shift was associated with irregular cycles among nulliparous women. Levels of menstrual and premenstrual distress, depressive symptoms, perceived stress, physical and mental fatigue, anxiety, and sleep problems were higher in women with irregular cycles than in those with regular cycles (p < 0.001, each). CONCLUSIONS: The study suggests that irregular and long menstrual cycles are associated with reproductive, lifestyle, and occupational factors; also with menstrual distress and perceived health status. Our findings contribute to a better understanding of potential risk factors for menstrual dysfunction, and thus, may help improve women's health.

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.

Subsequent menstrual disorder after spontaneous menarche in Turner syndrome.

OBJECTIVE: Turner syndrome (TS) is a congenital disease characterized by delayed puberty, ovarian dysgenesis and short stature. Although most patients are diagnosed with primary amenorrhea, approximately 15-20% of patients with TS are reported to have spontaneous menarche. However, little is known about their menstruation status after spontaneous menarche. In the current study, we investigated the menstrual abnormalities after spontaneous menarche in TS patients. DESIGN: Retrospective study. PATIENTS: This study included TS patients with spontaneous menarche at Osaka Police Hospital or Komura Women's Clinic between April 2015 and December 2019. MEASUREMENTS: Data regarding the age of menarche, menstruation status and chromosomal karyotype were collected and retrospectively analyzed. RESULTS: Of 172 TS patients, 32 with spontaneous menarche were identified. The median age of menarche was 12 years old. Premature ovarian insufficiency (POI) after menarche was observed in 12 patients (37.5%) and the median age at menopause was 20 years old. The average period from spontaneous menarche to menopause in these patients was 5.1 years. Five patients (15.6%) had irregular menstruation and 15 (46.9%) had regular menstruation. When examined according to the structural abnormality of the X chromosome, all patients with structural abnormality of the X chromosome were diagnosed with POI after spontaneous menarche, and none with mosaic without structural abnormality were diagnosed with POI. CONCLUSION: Approximately one-third of TS patients with spontaneous menarche were diagnosed with POI after menarche for an average of 5.1 years. Counseling is required for TS patients and their parents, including information about menstrual abnormalities or fertility preservation.

HYPOXIA AND REPRODUCTIVE HEALTH: The presence and role of hypoxia in the endometrium.

The endometrium is a multicellular tissue that is exquisitely responsive to the ovarian hormones. The local mechanisms of endometrial regulation to ensure optimal function are less well characterised. Transient physiological hypoxia has been proposed as a critical regulator of endometrial function. Herein, we review the literature on hypoxia in the non-pregnant endometrium. We discuss the pros and cons of animal models, human laboratory studies and novel in vivo imaging for the study of endometrial hypoxia. These research tools provide mounting evidence of a transient hypoxic episode in the menstrual endometrium and suggest that endometrial hypoxia may be present at the time of implantation. This local hypoxia may modify the inflammatory environment, influence vascular remodelling and modulate endometrial proliferation to optimise endometrial function. Finally, we review current knowledge of the impact of this hypoxia on endometrial pathologies, with a focus on abnormal uterine bleeding. Throughout the manuscript areas for future research are highlighted with the aim of concentrating research efforts to maximise future benefits for women and society.

Effect of single- versus double-layer uterine closure during caesarean section on postmenstrual spotting (2Close): multicentre, double-blind, randomised controlled superiority trial.

OBJECTIVE: To evaluate whether double-layer uterine closure after a first caesarean section (CS) is superior compared with single-layer uterine closure in terms of postmenstrual spotting and niche development in the uterine caesarean scar. DESIGN: Multicentre, double-blind, randomised controlled superiority trial. SETTING: Thirty-two hospitals in the Netherlands. POPULATION: A total of 2292 women aged ≥18 years undergoing a first CS were randomly assigned to each procedure (1:1): 1144 women were assigned to single-layer uterine closure and 1148 women were assigned to double-layer uterine closure. METHODS: Single-layer unlocked closure and double-layer unlocked closure, with the second layer imbricating the first. MAIN OUTCOME MEASURES: Number of days with postmenstrual spotting during one menstrual cycle 9 months after CS. SECONDARY OUTCOMES: perioperative and menstrual characteristics; transvaginal ultrasound measurements. RESULTS: A total of 774 (67.7%) women from the single-layer group and 770 (67.1%) women from the double-layer group were evaluable for the primary outcome, as a result of drop-out and amenorrhoea. The mean number of postmenstrual spotting days was 1.33 (bootstrapped 95% CI 1.12-1.54) after single-layer closure and 1.26 (bootstrapped 95% CI 1.07-1.45) after double-layer closure (adjusted mean difference -0.07, 95% CI -0.37 to 0.22, P = 0.810). The operative time was 3.9 minutes longer (95% CI 3.0-4.9 minutes, P < 0.001) and niche prevalence was 4.7% higher (95% CI 0.7-8.7%, P = 0.022) after double-layer closure. CONCLUSIONS: The superiority of double-layer closure compared with single-layer closure in terms of postmenstrual spotting after a first CS was not shown. Long-term obstetric follow-up of our trial is needed to assess whether uterine caesarean closure guidelines should be adapted. TWEETABLE ABSTRACT: Double-layer uterine closure is not superior for postmenstrual spotting after a first caesarean; single-layer closure performs slightly better on other outcomes.

Clinical Presentation and Diagnosis of Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy with many clinical manifestations. The effects on women's lives start at puberty and can last throughout her lifetime. Women frequently experience anovulatory menstrual cycles, infertility, hirsutism, obesity and increased risk of diabetes mellitus, hypertension, lipid abnormalities, and metabolic syndrome. PCOS is a heterogenous disorder, and a diagnosis of exclusion. In general, women afflicted will have menstrual irregularities, ultrasound findings of abnormal ovarian size and morphology, and clinical or laboratory evidence of hyperandrogenism. This chapter reviews the current understanding of PCOS, associated metabolic abnormalities, and diagnosis in reproductive-aged women, as well as adolescents.

Effects of past environmental tobacco smoke exposure on the menstrual cycle and menstrual phase-related symptoms: A cross-sectional study.

AIM: This study examined the effects of current and past environmental tobacco smoke exposure on the menstrual cycle and menstrual phase-related symptoms in nonsmoking Japanese women of child-bearing age. METHODS: Of 5000 women who agreed to participate, 3935 were analyzed (932 smokers, 2326 nonsmokers, and 677 past smokers). Nonsmokers were divided into three groups based on smoking status and environmental tobacco smoke exposure: nonsmokers without exposure (n = 352), nonsmokers with past exposure (n = 1196) and nonsmokers with current exposure (n = 778). Participants completed a questionnaire on background characteristics, environmental tobacco smoke exposure (location and relationship to smokers), abnormal menstrual cycle, days of menstrual cycle and menstrual cycle-related symptoms experienced in the past 3 months (assessed by the Menstrual Distress Questionnaire). RESULTS: Mean age was 29.7 ± 7.0 (20-44) years. Compared with nonsmokers without environmental tobacco smoke exposure, current smokers had the highest risk of an abnormal menstrual cycle (adjusted odds ratio [OR], 1.74 [1.194-2.545]), followed by nonsmokers with past exposure (adjusted OR, 1.70 [1.171-2.464]), past smokers (adjusted OR, 1.60 [1.081-2.366]) and nonsmokers with current environmental tobacco smoke exposure (adjusted OR, 1.49 [0.901-1.212]). Irrespective of environmental tobacco smoke exposure, current smokers reported significantly more severe premenstrual and menstrual symptoms than nonsmokers, and nonsmokers with past environmental tobacco smoke exposure had significantly more severe premenstrual and menstrual symptoms than nonsmokers without environmental tobacco smoke exposure. CONCLUSION: Past environmental tobacco smoke exposure, especially during childhood or adolescence, might harm women's reproductive health when they reach reproductive age.

Obesity, menstrual irregularity and polycystic ovary syndrome in young women with type 1 diabetes: A population-based study.

BACKGROUND: Type 1 diabetes (T1D) is associated with reproductive dysfunction, particularly in the setting of poor metabolic control. Improvements in contemporary management ameliorate these problems, albeit at the cost of increased exogenous insulin and rising obesity, with emerging reproductive implications. OBJECTIVE: To evaluate changes in body mass index (BMI) and the relationship between obesity, menstrual irregularity and polycystic ovary syndrome (PCOS) in young women with T1D, compared with controls. METHODS: Longitudinal observational study using data from the Australian Longitudinal Study in Women's Health of the cohort born in 1989-95, from 2013 to 2015. Three questionnaires administered at baseline and yearly intervals were used to evaluate self-reported menstrual irregularity, PCOS and BMI. RESULTS: Overall, 15 926 women were included at baseline (T1D, n = 115; controls, n = 15 811). 61 women with T1D and 8332 controls remained at Year 2. Median BMI was higher in women with type 1 diabetes (25.5 vs 22.9 kg/m2 , P < .001), where over half were overweight or obese (54.4% vs 32.9%, P < .001). Median BMI increased by 1.11 and 0.45 kg/m2 , in the T1D and control groups, respectively. T1D was independently associated with an increased risk of menstrual irregularity (RR 1.22, 95% CI 1.02-1.46) and PCOS (RR 2.41, 95% CI 1.70-3.42). Obesity conferred a 4-fold increased risk of PCOS, compared to those with normal BMI (RR 3.93, 95% CI 3.51-4.42). CONCLUSIONS: Obesity is prevalent amongst women with T1D and may be a key contributor to the higher risk of menstrual irregularity and PCOS in this cohort, representing an important opportunity for prevention and intervention.

Associations of childhood adiposity with menstrual irregularity and polycystic ovary syndrome in adulthood: the Childhood Determinants of Adult Health Study and the Bogalusa Heart Study.

STUDY QUESTION: Is high adiposity in childhood associated with menstrual irregularity and polycystic ovary syndrome (PCOS) in later life? SUMMARY ANSWER: Overall, greater childhood BMI was associated with menstrual irregularity, and greater childhood BMI and waist/height ratio (WHtR) in white but not black participants were associated with PCOS in adulthood. WHAT IS KNOWN ALREADY: Increased childhood BMI has been associated with irregular menstrual cycles and PCOS symptoms in adulthood in two longitudinal population-based studies, but no study has reported on associations with childhood abdominal obesity. Few studies have investigated whether there are racial differences in the associations of adiposity with PCOS though there has been some suggestion that associations with high BMI may be stronger in white girls than in black girls. STUDY DESIGN, SIZE, DURATION: The study included 1516 participants (aged 26-41 years) from the Australian Childhood Determinants of Adult Health study (CDAH) and 1247 participants (aged 26-57 years) from the biracial USA Babies substudy of the Bogalusa Heart Study (BBS) who were aged 7-15 years at baseline. At follow-up, questions were asked about menstruation (current for CDAH or before age 40 years for BBS), ever having had a diagnosis of PCOS and symptoms of PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: In CDAH, a single childhood visit was conducted in 1985. In BBS, multiple childhood visits occurred from 1973 to 2000 and race was reported (59% white; 41% black). In childhood, overweight and obesity were defined by international age-sex-specific standards for BMI and WHtR was considered as an indicator of abdominal obesity. Multilevel mixed-effects Poisson regression estimated relative risks (RRs) adjusting for childhood age, highest parental and own education and age at menarche. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of childhood obesity was 1.1% in CDAH and 7.5% in BBS. At follow-up, menstrual irregularity was reported by 16.7% of CDAH and 24.5% of BBS participants. The prevalence of PCOS was 7.4% in CDAH and 8.0% in BBS participants. In CDAH, childhood obesity was associated with menstrual irregularity (RR = 2.84, 95% CI: 1.63-4.96) and PCOS (RR = 4.05, 95% CI: 1.10-14.83) in adulthood. With each 0.01 unit increase in childhood WHtR there was a 6% (95% CI: 1-11%) greater likelihood of PCOS. Overall, in BBS, childhood obesity was associated with increased risk of menstrual irregularity (RR = 1.44, 95% CI: 1.08-1.92) in adulthood. Significant interaction effects between race and childhood adiposity were detected in associations with PCOS. In BBS white participants, childhood obesity was associated with PCOS (RR = 2.93, 95% CI: 1.65-5.22) and a 0.01 unit increase in childhood WHtR was associated with an 11% (95% CI: 5-17%) greater likelihood of PCOS in adulthood. In BBS black participants, no statistically significant associations of childhood adiposity measures with PCOS were observed. LIMITATIONS, REASONS FOR CAUTION: The classification of menstrual irregularity and PCOS was based on self-report by questionnaire, which may have led to misclassification of these outcomes. However, despite the limitations of the study, the prevalence of menstrual irregularity and PCOS in the two cohorts was consistent with the literature. While the study samples at baseline were population-based, loss to follow-up means the generalizability of the findings is uncertain. WIDER IMPLICATIONS OF THE FINDINGS: Greater childhood adiposity indicates a higher risk of menstrual irregularity and PCOS in adulthood. Whether this is causal or an early indicator of underlying hormonal or metabolic disorders needs clarification. The stronger associations of adiposity with PCOS in white than black participants suggest that there are racial differences in childhood adiposity predisposing to the development of PCOS and other environmental or genetic factors are also important. STUDY FUNDING/COMPETING INTEREST(S): The CDAH study was supported by grants from the Australian National Health and Medical Research Council (grants 211316, 544923 and 1128373). The Bogalusa Heart Study is supported by US National Institutes of Health grants R01HD069587, AG16592, HL121230, HD032194 and P50HL015103. No competing interests existed.

Hyperprolactinemia as a prognostic factor for menstrual disorders in female adolescents with advanced chronic kidney disease.

BACKGROUND: In adolescents with chronic kidney disease (CKD), menstrual disorders (MD) are common, which can make the management of CKD difficult and can sometimes delay renal transplantation. This study aimed to identify the usefulness of hormonal measurements in adolescents with CKD and their relationships with MD during a 1-year follow-up. METHODS: A prospective cohort study was designed. Adolescents with CKD stages IV and V were included. Through clinical files and via interview, the ages at puberty onset, menarche and the date of last menstruation were identified. A 1-year follow-up was conducted over a menstrual cycle calendar. At the beginning of follow-up, routine hormonal profiles (thyroid profiles, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol) were assessed. We compared the hormonal profiles of the patients with and without MD (wMD vs. woMD). Comparisons between groups were made by Wilcoxon and Fisher's tests. Logistic regression analysis was used. RESULTS: Fifty-seven patients, including 30 patients classified as wMD, were analyzed. The median age was 15 years, and the median time of CKD evolution was 18 months. There were no differences in general and biochemical characteristics between patients wMD and woMD. In terms of hormonal measurements, the levels of thyroid-stimulating hormone (TSH) and prolactin were higher in the wMD patients. A prolactin level ≥ 36.8 ng/ml was a risk factor for presenting with MD (RR 34.4, p = 0.002). CONCLUSIONS: Hyperprolactinemia is correlated with MD in adolescents with CKD.

Menstrual problems in adolescence: relationship to serum vitamins A and E, and systemic inflammation.

BACKGROUND: Vitamin status and inflammatory mechanisms may be related to menstrual cycle abnormalities. We investigated the associations between serum fat soluble vitamin (vitamins A and E) concentrations and biomarkers of inflammation and antioxidant status with menstrual characteristics, primary dysmenorrhea (PD) and premenstrual syndrome (PMS) in healthy adolescents. METHODS: A total of 897 adolescent girls either suffering from PMS (n = 134), PD (n = 322), PMS and PD (n = 293) or healthy adolescents (n = 148) were recruited. Serum vitamin A and E, high-sensitivity C-reactive protein (hs-CRP), antibody titers to Hsp27 (anti-Hsp27), serum prooxidant-antioxidant balance (PAB), WBC, mean platelet volume (MPV), and platelet distribution width (PDW) and RBC distribution width (RDW) were measured. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and RDW-to-platelet ratio (RPR) were calculated. RESULTS: Girls with long bleeding periods had lower concentrations of serum vitamin E compared to those who reported a normal period duration. There were significantly differences between the groups reporting oligomenorrhea, regular menses and polymenorrhea with respect to NLR, RPR, MPV and PDW. Logistic regression demonstrated that the presence of both PMS and PD was positively related to higher serum hs-CRP, PAB and NLR, while serum vitamin A level was inversely related to the presence of PMS. CONCLUSIONS: We found that serum vitamin A, hs-CRP, PAB and NLR are significantly associated with the presence of PMS and PD. Inflammatory processes may contribute to the etiology, symptoms and severity of menstrual disorders. Prospective studies are needed to elucidate the possibility of targeting oxidative stress and inflammatory process for the amelioration of menstrual symptoms.