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.

Assessment of medication adherence in children and adults with congenital adrenal hyperplasia and the impact of knowledge and self-management.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is caused by a deficiency of one of the enzymes required for cortisol biosynthesis. The disease is classified as either classic (severe phenotype), subdivided into simple virilizing (SV) and salt-wasting (SW), or non-classic (NC) CAH. The treatment regime involves life-long glucocorticoid replacement, especially in classic phenotype. OBJECTIVES: We aimed to assess medication adherence, endocrine knowledge and self-management in patients with CAH and to compare patients' and physicians' assessments of medication adherence. METHODS: A prospective cross-sectional study of 108 patients with CAH (52 children and 56 adults) and 45 parents/caregivers. Two adherence measures were used, a self-reported questionnaire named Adherence Starts with Knowledge (ASK-12) with a cut-off level > 22 defined as poor adherence rate, and an assessment by a physician based on growth rate, 17-hydroxyprogesterone profile, and medical history, ranked using a five-point Likert scale. Measurements of the patients'/parents' knowledge and self-management were performed using Endocrine Society Clinical Practice Guidelines. RESULTS: Self-reported medication adherence was good with 74% of the participants reported good adherence with higher adherence in patients with the SW form. The highest endocrine knowledge and self-management were found in parents compared with children and adults with classic CAH. There was 30% discordance between the assessments by a physician and the self-reported ASK-12 scores independent of the severity of CAH. CONCLUSION: Patients and endocrinologists reported high medication adherence, however, discordance was found in 30% of the studied patients. Patients with the more severe form of CAH had higher adherence rates and demonstrated good endocrine knowledge/self-management.

Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.

BACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS: We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. FINDINGS: Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. INTERPRETATION: The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. FUNDING: Merck & Co, Inc.

Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement in overweight polycystic ovary syndrome-Substudy of randomized trial between diet, exercise and diet plus exercise for weight control.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is commonly affected by obesity. PCOS phenotypes are prone to increased waist/hip ratio, insulin resistance and dyslipidaemia. This substudy was undertaken to evaluate the effects of lifestyle interventions on metabolic biomarkers in overweight/obese PCOS women and the interventional effects of dietary components related to metabolic outcomes. DESIGN: Randomized three-arm parallel study. PATIENTS: Fifty-seven PCOS women body mass index (BMI >27 kg/m2 , age 18-40) were randomly assigned to diet (D, n = 19), exercise (E, n = 19) or diet plus exercise (DE, n = 19) in three-arm fashion over 16 weeks. The D group received nutritional counselling by a dietician to reduce their energy intake by at least 600 kcal/d. The E group received an ambulatory exercise regimen from a physiotherapist. The DE group had both interventions. MEASUREMENTS: Self-reported food intake over 4 days, exercise pedometers, BMI, waist/hip ratio, blood pressure, body composition and oral glucose tolerance test were performed before and at the end of intervention. RESULTS: BMI, waist circumference and total cholesterol were significantly reduced in the D and DE groups, as well as low-density lipoprotein and Homeostasis Model of Assessment index in the D group. In the E group, exercise was increased along with a decrease in BMI and waist circumference. The strongest predictor of reduced BMI was increased fibre intake (-0.44, P = .03), while a decrease in trans fatty acid intake predicted reduced insulinogenic index (0.44, P < .01). CONCLUSIONS: Nutritional counselling with dieting is clearly effective to improve metabolic disturbances in overweight/obese women with PCOS. Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement and weight control.

Circulating androgens and SHBG during the normal menstrual cycle in two ethnic populations.

The objective of this study was to study possible ethnic differences in steroid hormones and sex hormone-binding globulin (SHBG) during the menstrual cycle. Serum levels of the ovarian steroids estradiol (E2) and progesterone (P) and of follicle-stimulating hormone (FSH), luteinizing hormone (LH), SHBG, dehydroepiandrosterone (DHEA) and testosterone (T-ria) were all measured by immunoassay during the menstrual cycle in 15 Swedish and 11 West Asian regularly menstruating women. Testosterone (T-ms) was also measured by LC-MS/MS and so were 4-androstene-3,17-dione (A-4) and 17-alpha-hydroxyprogesterone (17-OHP). There were no ethnic differences in levels of ovarian steroids, gonadotrophins, A-4, 17-OHP and T-ms. DHEA were significantly higher and SHBG significantly lower in West Asian than in Swedish women. Surprisingly, T-ria was significantly higher in West Asian than in Swedish women and higher than T-ms (47% in Swedish and 107% in West Asian women). The difference (T-ria - T-ms) showed strong positive correlations to DHEA in the total and in West Asian but not in Swedish women, indicating an influence of DHEA/DHEAS metabolites on the T-ria results. In conclusion, ethnic differences in cross reacting steroids may cause erroneous results in one ethnic group by a steroid immunoassay having reasonable specificity in another. The reasons for the lower SHBG and the higher DHEA levels in West Asian women are not known. The results raise the question about establishing different reference values for certain analytes in different ethnic groups.

Sex hormone levels as determinants of bone mineral density and osteoporosis in Vietnamese women and men.

This study sought to investigate the prevalence of osteoporosis and the role of sex hormone levels in the determination of bone mineral density (BMD) and osteoporosis in a Vietnamese population of women and men. The cross-sectional study involved 269 women and 222 men aged 13-83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of estradiol and testosterone were analyzed, and BMD was measured by dual X-ray absorptiometry. We found that the prevalence of osteoporosis in postmenopausal women was 18, 17, and 37 % for the femoral neck, total hip, and lumbar spine, respectively. For men aged 50 years or older, the corresponding values were 8, 7, and 12 %. In men, the most important predictors of BMD for the femoral neck and total hip were age, body mass index, and serum levels of estradiol. For the BMD of the lumbar spine, testosterone also had a significant influence. Determinants of osteoporosis in men for the total hip and lumbar spine were age, weight, and serum concentrations of estradiol and testosterone. In postmenopausal women, age, weight, and residence (urban vs rural) were the most important predictors of BMD and osteoporosis. For all women (including those of reproductive age), serum levels of estradiol were also significant. These data suggest that the prevalence of osteoporosis in the Vietnamese population is high also in men, and that estradiol levels are essential for bone mass in both men and women. The results should have clinical implications and increase awareness of an important health issue within Vietnamese society.

Prevalence and impact of vasomotor symptoms due to menopause among women in Brazil, Canada, Mexico, and Nordic Europe: a cross-sectional survey.

OBJECTIVE: This study investigated the prevalence and impact of moderate to severe vasomotor symptoms (VMS), related treatment patterns, and experiences in women. METHODS: The primary objective was to assess the prevalence of moderate to severe menopause-related VMS among postmenopausal women aged 40 to 65 years in Brazil, Canada, Mexico, and four Nordic European countries (Denmark, Finland, Norway, and Sweden) using an online survey. Secondary objectives assessed impact of VMS among perimenopausal and postmenopausal women with moderate to severe VMS using the Menopause-Specific Quality of Life questionnaire, Work Productivity and Activity Impairment questionnaire, Patient-Reported Outcomes Measurement Information System sleep disturbances assessment, and questions regarding treatment patterns and attitudes toward symptoms and available treatments. RESULTS: Among 12,268 postmenopausal women, the prevalence of moderate to severe VMS was about 15.6% and was highest in Brazil (36.2%) and lowest in Nordic Europe (11.6%). Secondary analyses, conducted among 2,176 perimenopausal and postmenopausal women, showed that VMS affected quality of life across all domains measured and impaired work activities by as much as 30%. Greater symptom severity negatively affected sleep. Many women sought medical advice, but most (1,238 [56.9%]) were not receiving treatment for their VMS. The majority (>70%) considered menopause to be a natural part of aging. Those treated with prescription hormone therapy and nonhormone medications reported some safety/efficacy concerns. CONCLUSIONS: Among women from seven countries, moderate to severe menopause-related VMS were widespread, varied by region, and largely impaired quality of life, productivity, and/or sleep.

Effects of oestrogen and testosterone therapy on serum metabolites in postmenopausal women.

OBJECTIVES: Metabolite profiles of body fluids or tissue extracts can be regarded as important indicators of physiological or pathological states. Whether hormone-specific alterations of the serum metabolome can be identified using this technique has not been tested yet. The aim of this study was to investigate metabolic responses during hormone therapy in postmenopausal women by a nontargeted metabolomics approach. METHODS: Sixty naturally postmenopausal women were randomly assigned to treatment with testosterone undecanoate 40 mg every second day; estradiol valerate 2 mg daily; or the combination of both. Serum metabolites were determined by gas chromatography-mass spectrometry (GC-MS) before and after 3 months of treatment. Metabolites affected by the treatment were identified and correlated with changes in insulin sensitivity and lipid profiles. RESULTS: Treatment-dependent and hormone-specific effects on serum metabolites were observed, ranging between 69% reduction and 184% increase, but the metabolites that best explained the differences could not be structurally identified. Effects on annotated metabolites were less associated with clinical parameters as compared to established serum markers for adverse lipid and carbohydrate metabolism, such as cholesterol and triglycerides. However, cystine, lysine and tyrosine were shown to change in correlation with insulin sensitivity and high-density lipoprotein cholesterol levels in response to testosterone, indicating that those responses were somehow related to each other. CONCLUSIONS: Oestrogen- and androgen-specific alterations in the serum metabolome could be identified using GC-MS, reflecting hormone-specific effects on whole body metabolism. New knowledge regarding steroid-mediated metabolic responses within different tissues might be obtained using a similar approach on tissue extracts.

Right-left digit ratios, a novel form of asymmetry: Patterns of instability in children and relationships to platelet counts and hospitalization in adults with COVID-19.

High right minus left (R-L) asymmetry of digit ratios has been reported to be linked to hospitalization for COVID-19. Here we examined the developmental patterns of this novel form of asymmetry in children and further explored their relationships to platelet counts and hospitalization for COVID-19 in adult patients. We considered ratios calculated from four digits (2D, 3D, 4D, 5D) in: (i) a sample of healthy participants aged 2 years to 18 years (n = 680, 340 males) and (ii) 96 adult patients (42 males) hospitalized for COVID-19 and 100 controls (53 males). The protocol for (ii) included a questionnaire and laboratory test results. In sample (i) of the six unsigned digit ratio asymmetries, those which included 5D had the highest mean asymmetry with the greatest between-individual variation and they were unstable over the age range of 2 years to 18 years. In sample (ii) patients showed higher asymmetries than controls in four ratios (2D:4D, 2D:5D, 3D:5D, 4D:5D) and a sum of asymmetries of the two independent ratios (2D:4D+3D:5D) correlated positively with platelet counts and hospitalization. Conclusion: Means and SDs of digit ratio asymmetry that include the 5th digit are high and age-unstable. Digit ratio asymmetry, particularly 5th digit ratio asymmetry and a composite measure of 2D:4D + 3D:5D asymmetry, may be positively linked to high platelet counts in COVID-19 patients and to an elevated risk of hospitalization.

Artificial intelligence deep learning model assessment of leukocyte counts and proliferation in endometrium from women with and without polycystic ovary syndrome.

OBJECTIVE: To study whether artificial intelligence (AI) technology can be used to discern quantitative differences in endometrial immune cells between cycle phases and between samples from women with polycystic ovary syndrome (PCOS) and non-PCOS controls. Only a few studies have analyzed endometrial histology using AI technology, and especially, studies of the PCOS endometrium are lacking, partly because of the technically challenging analysis and unavailability of well-phenotyped samples. Novel AI technologies can overcome this problem. DESIGN: Case-control study. SETTING: University hospital-based research laboratory. PATIENT(S): Forty-eight women with PCOS and 43 controls. Proliferative phase samples (26 control and 23 PCOS) and luteinizing hormone (LH) surge timed LH+ 7-9 (10 control and 16 PCOS) and LH+ 10-12 (7 control and 9 PCOS) secretory endometrial samples were collected during 2014-2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometrial samples were stained with antibodies for CD8+ T cells, CD56+ uterine natural killer cells, CD68+ macrophages, and proliferation marker Ki67. Scanned whole slide images were analyzed with an AI deep learning model. Cycle phase differences in leukocyte counts, proliferation rate, and endometrial thickness were measured within the study populations and between the PCOS and control samples. A subanalysis of anovulatory PCOS samples (n = 11) vs. proliferative phase controls (n = 18) was also performed. RESULT(S): Automated cell counting with a deep learning model performs well for the human endometrium. The leukocyte numbers and proliferation in the endometrium fluctuate with the menstrual cycle. Differences in leukocyte counts were not observed between the whole PCOS population and controls. However, anovulatory women with PCOS presented with a higher number of CD68+ cells in the epithelium (controls vs. PCOS, median [interquartile range], 0.92 [0.75-1.51] vs. 1.97 [1.12-2.68]) and fewer leukocytes in the stroma (CD8%, 3.72 [2.18-4.20] vs. 1.44 [0.77-3.03]; CD56%, 6.36 [4.43-7.43] vs. 2.07 [0.65-4.99]; CD68%, 4.57 [3.92-5.70] vs. 3.07 [1.73-4.59], respectively) compared with the controls. The endometrial thickness and proliferation rate were comparable between the PCOS and control groups in all cycle phases. CONCLUSION(S): Artificial intelligence technology provides a powerful tool for endometrial research because it is objective and can efficiently analyze endometrial compartments separately. Ovulatory endometrium from women with PCOS did not differ remarkably from the controls, which may indicate that gaining ovulatory cycles normalizes the PCOS endometrium and enables normalization of leukocyte environment before implantation. Deviant endometrial leukocyte populations observed in anovulatory women with PCOS could be interrelated with the altered endometrial function observed in these women.

Participant- and Clinician-Reported Long-Term Outcomes After Surgery in Individuals with Complete Androgen Insensitivity Syndrome.

STUDY OBJECTIVE: To evaluate the outcomes of genital surgery through participant's and observer's satisfaction with the anatomical and functional result. DESIGN AND SETTING: Multicenter cross-sectional study in 14 clinics in 6 European countries in 2014-2015. PARTICIPANTS: Seventy-one individuals with complete androgen insensitivity syndrome (≥16 years old). INTERVENTIONS: Data from clinical report files, an optional gynecological examination, patient-reported outcomes on received surgical interventions, satisfaction with appearance and function after surgery, and effect of the surgical procedure on life. MAIN OUTCOME MEASURES: Outcomes were calculated per different surgical treatments. Linear regression models were used for associations with vaginal satisfaction. RESULTS: Sixty-three participants had received surgery: 62 gonadectomies, 12 vaginal surgeries with or without vaginal dilations, 9 vaginal dilations only, and 2 breast enlargements. More than half of the participants took part in the gynecological examination. Vaginal length was similar in those without (60 mm) and with (67 mm) vaginoplasty and/or vaginal dilations. Participant- and observer-reported appearance of the genitals were generally satisfactory to good. Sexual complaints (pain or bleeding during/after intercourse) were common. Vaginal satisfaction was strongly associated with satisfaction with sex life in general, whereas vaginal interventions and number of surgeries were not. Many participants reported a negative effect of gonadectomy on their life. CONCLUSION: Despite good genital appearance, functional problems are commonly reported, across the different nonsurgical and surgical regimens. Patient-reported outcomes should be evaluated before and after surgical procedures. Because of the negative effect on life and the low risk of malignancy, gonadectomy should be deferred to adulthood with regular follow-up.

Ulipristal Acetate for Treatment of Premenstrual Dysphoric Disorder: A Proof-of-Concept Randomized Controlled Trial.

OBJECTIVE: Premenstrual dysphoric disorder (PMDD) is a common mood disorder, characterized by distressing affective, behavioral, and somatic symptoms in the late luteal phase of the menstrual cycle. The authors investigated continuous treatment with a selective progesterone receptor modulator, ulipristal acetate (UPA), as a potential treatment for PMDD. METHODS: The authors conducted an investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial in which women with PMDD (N=95) were treated with either 5 mg/day of UPA or placebo during three 28-day treatment cycles. The primary outcome was the change in premenstrual total score on the Daily Record of Severity of Problems (DRSP) from baseline to end of treatment. DRSP scores were captured by daily ratings using a smartphone application and were analyzed with linear mixed models for repeated measures. RESULTS: The mean improvement in DRSP score after 3 months was 41% (SD=18) in the UPA group, compared with 22% (SD=27) in the placebo group (mean difference -18%; 95% CI=-29, -8). Treatment effects were also noted for the DRSP depressive symptom subscale (42% [SD=22] compared with 22% [SD=32]) and the DRSP anger/irritability subscale (47% [SD=21] compared with 23% [SD=35]), but not for the DRSP physical symptom subscale. Remission based on DRSP score was attained by 20 women in the UPA group (50.0%) and eight women in the placebo group (21.1%) (a statistically significant difference). CONCLUSIONS: If these results are replicated, UPA could be a useful treatment for PMDD, particularly for the psychological symptoms associated with the disorder.

Self- and proxy-reported outcomes after surgery in people with disorders/differences of sex development (DSD) in Europe (dsd-LIFE).

BACKGROUND: Surgery is performed in many individuals with disorders/differences of sex development (DSD). Irreversibility of some surgical procedures, lack of information about the procedures, and lack of follow-up care for physical and psychological outcomes, lead to wish for more knowledge from both surgeons and patients. After the consensus conference in 2006, multidisciplinary care is provided to a higher degree with psychological support and more restricted surgical procedures. Outcome studies after genital surgery often lack of patient's perspective. OBJECTIVE: To describe surgical procedures in relation to diagnosis, to evaluate the outcomes of surgery through genital examination, and through patient's and observer's satisfaction with the anatomical and functional result after genital surgery. STUDY DESIGN: In a cross-sectional clinical study performed in six European countries in 2014/15, we have included 500 participants where surgery was performed, from a total of 1040 adolescents (≥16years) and adults with a DSD. Diagnoses included Turner syndrome (n = 301), mixed gonadal dysgenesis (45,XO/46,XY; n = 45), Klinefelter syndrome (n = 218), XYY (n = 1), 46, XY DSD (n = 222) and 46, XX DSD (n = 253). Study protocol included clinical report files, an optional gynecological or urological examination, patient reported outcomes including received surgical interventions, satisfaction with appearance and function after surgery, and impact of the surgical procedure on life. RESULTS: Five hundred participants had received genital or breast surgery, with the highest rate in 46, XY DSD and the lowest in Turner syndrome. Altogether; 240 participants had feminizing surgery, 112 had masculinizing surgery, and 217 underwent gonadectomy. Physicians evaluated anatomical appearance at genital examination as poor in less than 10%. Dissatisfaction with anatomical appearance was reported by 22% of the participants, dissatisfaction with function by 20%. Being (very) dissatisfied with anatomical appearance and function was reported by 13% of the study participants. Most participants reported no impact, or positive impact, of the surgical procedures on their lives, but 29% experienced a negative effect of gonadectomy on their life. DISCUSSION: There might be a selection bias and/or a recall bias for participating in our studies. Due to poor data quality about surgical procedures performed in the past, we also relied on participants memory about surgical procedures in their past. Ideally, patient reported outcomes should be evaluated both before and after surgical procedures. CONCLUSION: A vast majority are satisfied with appearance and function, but still genital or breast surgery have a long-lasting effect on patient's life. Self-reported satisfaction is usually lower than the observer's evaluation regarding both appearance and function.

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

OBJECTIVE: To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia. METHODS: This cross-sectional survey was conducted among 382 endocrinologists and obstetrician-gynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland, 18% in Denmark, 16% in Norway, 13% in Estonia, and 10% in Sweden or Iceland, and 75% were obstetrician-gynaecologists. Multivariable logistic regression models were run to identify health care provider characteristics for awareness, diagnosis and treatment of PCOS. RESULTS: Clinical features, lifestyle management and comorbidity were commonly recognized in women with PCOS, while impairment in psychosocial wellbeing was not well acknowledged. Over two-thirds of the physicians used the Rotterdam diagnostic criteria for PCOS. Medical endocrinologists more often recommended lifestyle management (OR = 3.6, CI 1.6-8.1) or metformin (OR = 5.0, CI 2.5-10.2), but less frequently OCP (OR = 0.5, CI 0.2-0.9) for non-fertility concerns than general obstetrician-gynaecologists. The physicians aged <35 years were 2.2 times (95% CI 1.1-4.3) more likely than older physicians to recommend lifestyle management for patients with PCOS for fertility concerns. Physicians aged 46-55 years were less likely to recommend oral contraceptive pills (OCP) for patients with PCOS than physicians aged >56 (adjusted odds ratio (OR) = 0.4, 95% CI 0.2-0.8). CONCLUSION: Despite well-organized healthcare, awareness, diagnosis and management of PCOS is suboptimal, especially in relation to psychosocial comorbidities, among physicians in the Nordic countries and Estonia. Physicians need more education on PCOS and evidence-based information on Rotterdam diagnostic criteria, psychosocial features and treatment of PCOS, with the recently published international PCOS guideline well needed and welcomed.

Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy complications. Epi-analysis of two previous randomised controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The aim of this third randomised trial (PregMet2) was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS. METHODS: PregMet2 was a randomised, placebo-controlled, double-blind, multicentre trial done at 14 hospitals in Norway, Sweden, and Iceland. Singleton pregnant women with PCOS aged 18-45 years were eligible for inclusion. After receiving information about the study at their first antenatal visit or from the internet, women signed up individually to participate in the study. Participants were randomly assigned (1:1) to receive metformin or placebo by computer-generated random numbers. Randomisation was in blocks of ten for each country and centre; the first block had a random size between one and ten to assure masking. Participants were assigned to receive oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1000 mg twice daily or placebo from week 2 until delivery. Placebo tablets and metformin tablets were identical and participants and study personnel were masked to treatment allocation. The primary outcome was the composite incidence of late miscarriage (between week 13 and week 22 and 6 days) and preterm birth (between week 23 and week 36 and 6 days), analysed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit. We also did a post-hoc individual participant data analysis of pregnancy outcomes, pooling data from the two previous trials with the present study. The study was registered with ClinicalTrials.gov, number NCT01587378, and EudraCT, number 2011-002203-15. FINDINGS: The study took place between Oct 19, 2012, and Sept 1, 2017. We randomly assigned 487 women to metformin (n=244) or placebo (n=243). In the intention-to-treat analysis, our composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0·50, 95% CI 0·22-1·08; p=0·08). We found no significant differences for our secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1·09, 95% CI 0·69-1·66; p=0·75). We noted no substantial between-group differences in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators. In the post-hoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group compared with 40 (10%) of 399 women in the placebo group (OR 0·43, 95% CI 0·23-0·79; p=0·004). INTERPRETATION: In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes. FUNDING: Research Council of Norway, Novo Nordisk Foundation, St Olav's University Hospital, and Norwegian University of Science and Technology.

Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance.

Elite athletic competitions have separate male and female events due to men's physical advantages in strength, speed, and endurance so that a protected female category with objective entry criteria is required. Prior to puberty, there is no sex difference in circulating testosterone concentrations or athletic performance, but from puberty onward a clear sex difference in athletic performance emerges as circulating testosterone concentrations rise in men because testes produce 30 times more testosterone than before puberty with circulating testosterone exceeding 15-fold that of women at any age. There is a wide sex difference in circulating testosterone concentrations and a reproducible dose-response relationship between circulating testosterone and muscle mass and strength as well as circulating hemoglobin in both men and women. These dichotomies largely account for the sex differences in muscle mass and strength and circulating hemoglobin levels that result in at least an 8% to 12% ergogenic advantage in men. Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases. Based on the nonoverlapping, bimodal distribution of circulating testosterone concentration (measured by liquid chromatography-mass spectrometry)-and making an allowance for women with mild hyperandrogenism, notably women with polycystic ovary syndrome (who are overrepresented in elite athletics)-the appropriate eligibility criterion for female athletic events should be a circulating testosterone of <5.0 nmol/L. This would include all women other than those with untreated hyperandrogenic disorders of sexual development and noncompliant male-to-female transgender as well as testosterone-treated female-to-male transgender or androgen dopers.

"It's Part of Me, Not All of Me": Young Women's Experiences of Receiving a Diagnosis Related to Diverse Sex Development.

STUDY OBJECTIVE: To understand young women's experiences of receiving a diagnosis related to diverse sex development. DESIGN: A qualitative narrative analysis of interviews. SETTING: Karolinska University Hospital. PARTICIPANTS: Nine women (aged 20-26 years) with complete androgen insensitivity syndrome, XY or XX gonadal dysgenesis. INTERVENTIONS: Semistructured interviews. MAIN OUTCOME MEASURES: A narrative approach was used to analyze the interviews. This involved identification of individual narratives of receiving the diagnosis, as well as identification of key issues that were common across interviews. RESULTS: The analysis showed how participants' prediagnosis life experiences framed how medical information was perceived upon diagnosis. All participants had been informed about their condition before the study, but not all remembered the name of their diagnosis. Participants described positive characteristics of health professionals, such as being flexible and able to adapt to patients' individual needs. Clinicians' strategies, such as normalizing patients' experiences, were usually perceived as supportive, but were not always considered helpful. After the diagnosis, participants were worried about potential social, practical, and philosophical issues. CONCLUSION: This research highlighted the importance of clinicians taking an exploratory and individualized approach to the sensitive process of disclosing a diagnosis related to diverse sex development to young adults. There are various strategies health professionals can use that might help young people to develop their knowledge about their condition: (1) repeating information to help the patient remember; (2) using language that is not too medicalized; and (3) communicating in a way that is meaningfully connected to patients' everyday lives.

Low aglycone content in commercial soy drink products.

The effectiveness of soy isoflavones to prevent bone loss in postmenopausal women is controversial. While consumption of soy in Vietnam is very high, we recently reported a prevalence of osteoporosis comparable to that of many Western populations. In the present study, we analyzed the isoflavone content of soy drink products commercially available in Vietnam and Sweden, and we also compared these products to "home-made" soy drink from beans of different origin. The amounts of the bioactive aglycones (daidzein, glycitein and genistein) and their glycoside isomers were quantified by high-pressure liquid chromatography. We found that the total isoflavone content was low in all preparations, around 70-100 mg/L and of this only 10% were bioactive aglycones. Of these, the Vietnamese products contained significantly lower levels of glycitein than the products from Sweden and "home-made" soy drink preparations. The results show that consumption of several liters of soy drink per day would be needed to achieve threshold levels for a protective effect on bone. There was no significant association between total protein and isoflavone content in different products. Accurate labeling of soy drink and other products eg of aglycone and glycoside content would allow health professionals and researchers to better explore the possible benefits of soy in dietary intervention studies.

Vitamin D deficiency in northern Vietnam: prevalence, risk factors and associations with bone mineral density.

PURPOSE: Vitamin D deficiency has been linked to osteoporosis and also to the risk of cancer, autoimmune disorders and cardiovascular diseases. This study sought to determine the prevalence of, and risk factors for, vitamin D deficiency and its relationship with bone mineral density (BMD) in a Vietnamese population. METHODS: This cross-sectional study involved 269 women and 222 men aged 13-83 years, who were randomly selected from urban and rural areas in northern Vietnam. Serum concentrations of 25-hydroxy-vitamin D [25(OH)D] and parathyroid hormone (PTH) were measured by electrochemiluminescence immunoassay. Vitamin D deficiency was defined as serum 25(OH)D levels below 20 ng/mL. BMD was measured by dual X-ray absorptiometry. RESULTS: The prevalence of vitamin D deficiency in women was 30%, almost two-fold higher than in men (16%). Significant predictors of vitamin D deficiency in women were urban residency (p<0.01) and age less than 30 years (p<0.01), whereas use of contraceptive pills was protective (p<0.01). In men, winter season was the only significant predictor of vitamin D deficiency (p<0.01). In multiple linear regression analysis, serum levels of 25(OH)D were positively associated with BMD in both women (p<0.001) and men (p<0.001). CONCLUSIONS: These data suggest that the prevalence of vitamin D deficiency is high in the Vietnamese population, and that part of this prevalence could be explained by low exposure to sunlight (urban residency and winter season). The high prevalence of vitamin D deficiency should raise the awareness of potentially important health issues such as osteoporosis within the Vietnamese society.

Women with bulimia nervosa exhibit attenuated secretion of glucagon-like peptide 1, pancreatic polypeptide, and insulin in response to a meal.

BACKGROUND: The eating disorder bulimia nervosa (BN) is characterized by frequent episodes of binge eating, followed regularly by inappropriate compensatory behavior, such as self-induced vomiting. OBJECTIVE: The current investigation was designed to examine possible alterations in the secretion of the gastrointestinal satiety peptides glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) in women with BN. DESIGN: Twenty-one women with BN and 17 healthy control subjects of comparable age and BMI were recruited. After fasting overnight, the subjects provided blood samples during ingestion of a standardized meal and self-rated their appetite on a visual analog scale. Fasting and meal-related secretion of the incretin GLP-1 and the meal-related feedback signal PP and insulin and glucose as indicators of the metabolic homeostasis were analyzed. RESULTS: Women with BN had significantly lower fasting and postprandial serum concentrations of GLP-1 (P < 0.01) and PP (P < 0.05) than did the control subjects. Furthermore, both the basal (P < 0.001) and peak (P < 0.05) concentrations of insulin were significantly attenuated in the bulimic subjects, whereas glucose concentrations were normal. As a consequence, the bulimic homeostasis model assessment of insulin index values were also lower (P < 0.001). CONCLUSIONS: Women with BN secrete abnormally low amounts of GLP-1 and PP, possibly because of the adaption to large meals in the form of enlarged gastric capacity and reduced muscle tone in the gastric wall. Attenuated secretion of these gastrointestinal satiety peptides may play a role in the maintenance of bulimic behavior.