Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency : a Swedish population-based national cohort study

CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. OBJECTIVE: This study aimed to study cardiovascular and metabolic morbidity in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. MAIN OUTCOME MEASURES: To study cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.Magn. Bergvalls FoundationKarolinska InstitutetStockholm County CouncilSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences, SIMSAM 340-2013-5867Manuscrip

Awareness of polycystic ovary syndrome among obstetrician-gynecologists and endocrinologists in Northern Europe

cited By 0Peer reviewe

Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome

Study Question What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference? Summary Answer International evidence-based guidelines including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. What Is Known Already Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. Study Design, Size, Duration International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. Participants/Materials, Setting, Methods Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis, and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. Main Results and the Role of Chance The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; ii) reducing unnecessary testing; iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. Limitations, Reasons for Caution Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. Wider Implications of the Findings The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. Study Funding/Competing Interest(S) The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREEII criteria and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC

Hormonal contraceptives do not impact economic preferences: Evidence from a randomized trial

A growing body of correlational studies suggests that sex hormones such as those contained in, or affected by, oral contraceptives (OCs) may impact economic behavior. However, despite widespread use of OCs among women in Western countries, little is known about their potential behavioral effects. The present study investigates whether OCs causally influence economic preferences. We randomly allocate 340 women aged 18–35 to three months of a widely used OC or placebo treatment. At the end of treatment, we conduct an economic experiment measuring altruism, financial risk taking, and willingness to compete. The statistical power is 80% to detect an effect size equal to a Cohen’s d of 0.30 at the 5% level. We find no significant effects of OCs on any of the measured preferences, indicating that this widely used OC treatment, commonly used throughout the world, does not significantly affect the measured economic preferences. Further, we find no relation between menstrual cycle phase and economic preferences in the placebo group.ISSN:0025-1909ISSN:1526-550

The perceived influence of menstrual cycle and hormonal contraceptives on training and performance: Comparison between football, handball, and orienteering

Recently, we published self-reported data concerning the perceived effects of the menstrual cycle and hormonal contraceptives on the training and performance of 1086 female athletes participating in 57 sports. However, studies comparing differences between sports with large sample sizes are lacking. The aim of this ancillary study was to compare the impact of the menstrual cycle and hormonal contraceptives on training and performance between the three largest sports in the cohort, that is, football, handball, and orienteering, as well as the knowledge and support provided to the female athletes engaged in these sports. The results are from a web-based questionnaire completed by 312 football players, 243 handball players, and 93 orienteers. A total of 54% of the orienteers planned their training based on the menstrual cycle, which was a higher proportion compared to football (45%) and handball (29%) players (p &lt; 0.05). Fewer football players believed that the menstrual cycle had an impact on their performance during training and competition compared to the two other sports. A high proportion of the athletes used hormonal contraceptives in all three sports, but a lower proportion of the orienteers (40%) used hormonal contraceptives compared to football (76%) and handball players (66%) (p &lt; 0.05). Football and handball players received overall more support than orienteers, and the support was mostly provided by a physiotherapist and/or a strength and conditioner coach besides the main coach. These findings demonstrate that the perceived influence of the menstrual cycle and hormonal contraceptives on training and performance differs between endurance athletes in orienteering compared to team-sport athletes in football and handball.Funder: Swedish Olympic Committé;Full text license: CC BY</p

Prevalence and correlates of current suicidal ideation in women with premenstrual dysphoric disorder

BACKGROUND: Although previous studies report an association between Premenstrual Dysphoric Disorder (PMDD) and suicidal ideation, most studies have only established a provisional and retrospective diagnosis of PMDD fundamentally invalidating the diagnosis. Therefore, the aim of this study was to describe the prevalence and to explore correlates of current suicidal ideation in the late luteal phase in women with prospectively assessed and confirmed PMDD. METHODS: Participants were 110 women who attended the pre-randomization baseline visit of two randomized placebo-controlled clinical trials between January 15, 2017 and October 19, 2019. PMDD was diagnosed prospectively in line with DSM-5 criteria. Current suicidal ideation was measured by the MADRS-S in the late luteal phase. Descriptive statistics were presented and logistic regression analyses were carried out to explore the association between psychosocial and health characteristics and current suicidal ideation, presenting unadjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Current suicidal ideation was reported by nearly 40% of women with confirmed PMDD (n = 43, 39.1%). Previous psychological treatment for PMDD and higher depressive symptoms in the late luteal phase were positively associated with current suicidal ideation (OR 5.63, 95% CI 1.07-29.49, and OR 1.17, 95% CI 1.10-1.25, respectively), whereas higher ratings of self-rated health were associated with lower odds ratios for current suicidal ideation (OR 0.98, 95% CI 0.96-0.99). CONCLUSIONS: A substantial proportion of women with confirmed PMDD report current suicidal ideation in the late luteal phase. Results point to a need for better awareness and screening of suicidal ideation in women with PMDD

Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer

Human cytomegalovirus (HCMV) has been detected in various types of tumors. We studied the prevalence of HCMV in ovarian cancer and its relation to clinical outcome. Paraffin-embedded tissues obtained prospectively from 45 patients with ovarian cancer and 30 patients with benign ovarian cystadenoma were analyzed for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Plasma was analyzed for HCMV serology. HCMV-IgG levels were higher in patients with ovarian cancer or benign cystadenoma than in age-matched controls (P = .002, P < .0001, respectively). HCMV IgM was detected in 12% of ovarian cancer patients and 3% of patients with benign tumors but was absent in controls. In patients with ovarian cancer, higher IgG levels were associated with better outcomes (P = .04). Extensive HCMV-IE protein expression was detected in 75% of ovarian cancers and 26% of benign tumors; pp65 was detected in 67% of ovarian cancers and 14% of benign tumors. A higher grade of HCMV infection was associated with higher stage of disease. Extensive HCMV-pp65 expression was associated with shorter median overall survival than focal expression (39 versus 42.5 months, P = .03). At study closure, 58% of ovarian cancer patients with focal pp65 expression were alive versus 27% of patients with extensive pp65 expression (P = .03). Thus, HCMV proteins are detected at different levels in ovarian tumors and benign cystadenomas. Ovarian cancer patients with focal HCMV-pp65 expression in their tumors and high IgG levels against HCMV lived longer, highlighting a need for in-depth studies of the oncomodulatory role of HCMV in ovarian cancer

The Biological Basis of Sex Differences in Athletic Performance: Consensus Statement for the American College of Sports Medicine

Biological sex is a primary determinant of athletic performance because of fundamental sex differences in anatomy and physiology dictated by sex chromosomes and sex hormones. Adult men are typically stronger, more powerful, and faster than women of similar age and training status. Thus, for athletic events and sports relying on endurance, muscle strength, speed, and power, males typically outperform females by 10%–30% depending on the requirements of the event. These sex differences in performance emerge with the onset of puberty and coincide with the increase in endogenous sex steroid hormones, in particular testosterone in males, which increases 30-fold by adulthood, but remains low in females. The primary goal of this consensus statement is to provide the latest scientific knowledge and mechanisms for the sex differences in athletic performance. This review highlights the differences in anatomy and physiology between males and females that are primary determinants of the sex differences in athletic performance and in response to exercise training, and the role of sex steroid hormones (particularly testosterone and estradiol). We also identify historical and nonphysiological factors that influence the sex differences in performance. Finally, we identify gaps in the knowledge of sex differences in athletic performance and the underlying mechanisms, providing substantial opportunities for high-impact studies. A major step toward closing the knowledge gap is to include more and equitable numbers of women to that of men in mechanistic studies that determine any of the sex differences in response to an acute bout of exercise, exercise training, and athletic performance

Exercise recommendations for women with polycystic ovary syndrome : Is the evidence enough?

In this opinion piece, we summarize, discuss implications of implementation, and critically evaluate our 2018 evidence-based guideline recommendations for exercise and physical activity in women with polycystic ovary syndrome (PCOS). We developed recommendations as part of a larger international guideline development project. The overall guideline scope and priorities were informed by extensive health professional and consumer engagement. The lifestyle guideline development group responsible for the exercise recommendations included experts in endocrinology, exercise physiology, gynecology, dietetics, and obstetrics, alongside consumers. Extensive online communications and two face-to-face meetings addressed five prioritized clinical questions related to lifestyle, including the role of exercise as therapy for women with PCOS. The guideline recommendations were formulated based on one narrative and two evidence-based reviews, before consensus voting within the guideline panel. The development process was in accordance with the Appraisal of Guidelines for Research and Evaluation (AGREE) II, and used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework to assess evidence quality, desirable and undesirable consequences, feasibility, acceptability, cost, implementation, and recommendation strength. Given the evidence for exercise as therapy in PCOS being of low quality, a consensus recommendation was made based on current exercise guidelines for the general population. Women with PCOS and clinicians are forced to adopt generic approaches when recommending exercise therapy that perpetuates clinical management with pharmacological solutions. The current status of evidence highlights the need for greater international co-operation between researchers and funding agencies to address key clinical knowledge gaps around exercise therapy in PCOS to generate evidence for appropriate, scalable, and sustainable best practice approaches