The prevalence patterns and risk factor profiles of poor muscle health and its associated components in multiethnic older Asians: The PIONEER study.

BACKGROUND: We aim to determine the multiethnic patterns of the prevalence and associated factors of poor muscle health and its associated components in older Chinese, Malays, and Indian Asian adults. METHODS: We included 2199 participants (mean age ± SD: 72.9 ± 8.3 years; 54.3% female) from the baseline assessment of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER; 2017-2022) cohort study. Poor muscle health was defined as the presence of either low muscle mass (DEXA), or low muscle strength (handgrip strength), or low physical performance (gait speed). Its components include poor muscle function (low muscle strength and/or low physical performance without low muscle mass), pre-sarcopenia (low muscle mass only), and any sarcopenia (low muscle mass with low muscle strength and/or low physical performance). Sociodemographic, clinical, and lifestyle factors were assessed using biochemistry, clinical tests, and validated questionnaires. Regression models were utilized to evaluate the independent risk factors of poor muscle health and its components. RESULTS: The national census-adjusted prevalence of poor muscle health (88%) was similar across the three ethnic groups. However, Chinese individuals had higher prevalence of pre-sarcopenia and any sarcopenia, and a lower prevalence of poor muscle function compared with Indians or Malays. We observed ethnic differences in modifiable risk factors (low physical activity, diabetes, osteoporosis, and obesity) of poor muscle health and its components. Although obesity was protective of pre-sarcopenia (RRR = 0.19, 95% CI: 0.11, 0.36) and any sarcopenia (RRR = 0.29, 95% CI: 0.18, 0.47) in the overall population and across ethnic groups, it was associated with 1.7 times (95% CI: 1.07, 2.67) the likelihood of poor muscle function in the entire population. CONCLUSIONS: Almost 90% of community dwelling Singaporean aged ≥60 years have poor muscle health across the three ethnic groups with ethnic disparities in modifiable risk factors, highlighting an urgent need for community-wide targeted interventions to promote muscle health.

Associations between hypertension with reproductive and menopausal factors: An integrated women's health programme (IWHP) study.

BACKGROUND: Women are less likely to have classic cardiovascular risk factors than men, and events during their reproductive and menopausal years may increase hypertension risk. The aim of this study is to examine woman-specific factors, including menstrual, reproductive and pregnancy complications, in relation to the prevalence of hypertension in mid-life Asian women. METHODS: This is a cross-sectional study of 1146 healthy women aged 45-69 years, from a multi-ethnic Asian cohort. The women completed an extensive questionnaire that included their sociodemographic details, medical history, lifestyle and physical activity, and reproductive and menopausal history. They also underwent objectively measured physical performance tests and a dual X-ray absorptiometry scan. Hypertension was defined as a systolic BP ≥140 and/or diastolic BP ≥90mm Hg, past diagnosis by a physician, or use of antihypertensive medications. Multivariable logistic regression was used to assess the independent risk factors for hypertension. RESULTS: The average age of the 1146 women analysed was 56.3 (SD 6.2) years, and 55.2 percent of them were hypertensive. The prevalence of gestational diabetes and gestational hypertension was 12.6% and 9.4%, respectively. Besides age, abnormal menstrual cycle length at 25 years of age (OR:2.35, CI:1.34-4.13), preeclampsia (OR:2.46, CI:1.06-5.74), increased visceral adiposity (OR:4.21, CI:2.28-7.79) and reduced physical performance (OR:2.83, CI:1.46-5.47) were independently associated with hypertension in Asian women. CONCLUSIONS: Our findings highlight the necessity of including features of menstrual and reproductive history as possible indicators of hypertension risk in cardiovascular disease risk assessment and prevention among Asian women. Reducing visceral adiposity and exercise to improve physical performance may help women avoid developing hypertension.

Individual and combined associations of sarcopenia, osteoporosis and obesity with frailty in a multi-ethnic asian older adult population.

BACKGROUND: We explored the relationships between sarcopenia (SP), osteoporosis (OP), obesity (OB), (alone and in combination) with physical frailty (PF) in a multi-ethnic, population-based study of Asians aged ≥ 60 years. METHODS: Participants were enrolled from the PopulatION HEalth and Eye Disease PRofile in Elderly Singaporeans Study (PIONEER) study. PF was defined using the modified Fried phenotype; SP using the Asian Working Group for Sarcopenia 2019; OP using bone mineral density scores; and OB using the fat mass index. Modified Poisson regression models investigated the associations between exposures and PF, and the relative excess rates of PF due to interactions (RERI) to determine synergistic or antagonistic interactions. RESULTS: Of the 2643 participants, 54.8% was female; and 49.8%, 25.1%, 25.0% were Chinese, Indians, and Malays, respectively. 25%, 19.0% and 6.7% participants had OB only, SP only, and OP only, respectively. A total of 356 (17.5%), 151 (7.4%) and 97 (4.8%) had osteosarcopenia (OSP), sarcopenic obesity (SOB) and osteo-obesity (OOB), respectively; while 70 (3.5%) had all 3 morbid conditions (osteosarcopenic obesity, OSO). Both SP only and OB only were strongly associated with increased rates of PF (RR: 2.53, 95% CI: 1.95, 3.29; RR: 2.05, 95% CI: 1.58, 2.66 respectively); but not OP. Those with OSP, OOB and SOB were also associated with high risks of PF (RR: 2.82, 95% CI: 2.16, 3.68; RR: 2.34, 95% CI: 1.69, 3.23; and RR: 2.58, 95% CI: 1.95, 3.41, respectively) compared to robust individuals. Critically, individuals with OSO had the highest relative risk of having PF (RR: 3.06, CI: 2.28, 4.11). Only the sarcopenia-obesity interaction was significant, demonstrating negative synergism (antagonism). The concurrent presence of SP and OB was associated with a 100% lower rate of PF compared to the sum of the relatively rates of SP only and OB only. CONCLUSION: The prevalence of SP, OB and OP, alone and combined, is substantial in older Asians and their early identification is needed to mitigate the risk of frailty. OB may interact with SP in an antagonistic manner to moderate rates of frailty. Further longitudinal studies are needed to address causality and mechanistic underpinnings our findings.

Menopausal symptoms in midlife Singaporean women: Prevalence rates and associated factors from the Integrated Women's Health Programme (IWHP).

OBJECTIVE: Menopausal symptoms can substantially impact quality of life. We studied somatic, psychological, and urogenital symptoms and their associated factors. DESIGN: Cross-sectional study of healthy midlife Singaporean women from three major Asian ethnic groups. METHODS: In 2014-16, women aged 45 to 69 attending well-woman clinics at the National University Hospital Singapore completed the Menopause Rating Scale (MRS). Sociodemographic, reproductive, medical, anthropometric, body composition, and physical performance characteristics were assessed using validated questionnaires and strict protocols. We analysed sub-scales and total scores by median split, and adjusted odds ratios using multivariable logistic regression. RESULTS: Of the 1054 eligible women, 62.6 % reported at least one moderate to extremely severe symptom. The top five menopausal symptoms were joint and muscle discomfort, sleep problems, vaginal dryness, physical and mental exhaustion, and hot flushes. Higher total scores on the MRS were associated with moderate disability (adjusted odds ratio: 9.80, 95 % confidence interval: 2.88-33.34), poorer self-rated health status (2.18, 1.60-2.97), menstrual irregularity at 25 years (1.63, 1.07-2.49), and slower chair stands (1.49, 1.09-2.03). Age ≥65 (0.54, 0.30-0.94) and a lower level of education (0.45, 0.26-0.76) had significant inverse associations with total MRS score. CONCLUSIONS: Menopausal symptoms were associated with disability, poorer health status, and weaker lower-body muscle strength. These data add to the limited Asian evidence and raise the profile of this important area of health.

Associations of reading language preference with muscle strength and physical performance: Findings from the Integrated Women's Health Programme (IWHP).

BACKGROUND: The contribution of language preference and ethnicity to muscle strength and physical performance is unclear. We examined the associations of reading language preferences with muscle strength and performance in Chinese women and compared them to other ethnicities. METHODS: The Integrated Women's Health Programme (IWHP) cohort comprised community-dwelling, midlife Singaporean women aged 45-69. Ethnic Chinese women could choose between the English or Chinese versions of the questionnaire. Malay and Indian women were presented with the English version. Sociodemographic, reproductive, anthropometric characteristics were obtained. Hand grip strength and physical performance were objectively assessed. Visceral adiposity (VAT) was determined by Dual-energy X-ray Absorptiometry. Multivariable logistic regression models were used to determine independent associations of language preference/ethnicity with muscle strength and physical performance. RESULTS: The cohort comprised 1164 women (mean age: 56.3±6.2 years); 84.1% Chinese, 5.6% Malay, and 10.3% Indian. 315 Chinese participants (32.2%) had a Chinese-language reading preference (CLP). CLP women tended to be parous, of a lower socioeconomic status (lower proportions received tertiary education, lower employment rates and lower household income), and engaged in less physical activity compared to Chinese women with an English-language preference (ELP). This translated to a weaker hand grip strength (aOR: 1.56; 95%CI: 1.07-2.27), slower repeated chair stand (1.55; 1.12-2.13), poorer balance on tandem stand (2.00; 1.16-3.47), and a slower gait speed (1.62; 1.06-2.47). Compared to ELP women, Malay women had higher odds of poor hand grip strength (1.81; 1.12-2.93) while Indians had a higher odd of poor balance on one-leg stand (2.12; 1.28-3.52) and slow gait speeds on usual (1.88; 1.09-3.25) and narrow walks (1.91; 1.15-3.17). CONCLUSIONS: Chinese language reading preference was associated with inferior muscle strength and physical performance. Such disparities were largest and most consistent in the CLP group, followed by Indian and Malay women compared to the ELP group. Further studies should determine if CLP-associated muscle weakness can predict adverse health outcomes.

Factors associated with deep infiltrating endometriosis, adenomyosis and ovarian endometrioma.

INTRODUCTION: To compare epidemiological features and clinical presentations of deep infiltrating endometriosis with endometrioma and adenomyosis, as well as to identify risk factors for the respective histologically confirmed conditions. METHOD: Patients undergoing index surgery at the National University Hospital, Singapore for endometriosis or adenomyosis over a 7-year period-from 2015 to 2021-were identified from hospital databases using the Table of Surgical Procedures coding. Social and epidemiological features of cases with histologically confirmed diagnoses of endometrioma only, adenomyosis only, and deep infiltrating endometriosis were compared. Significant variables from univariate analysis were entered into 3 binary multivariate logistic regression models to obtain independent risk factors for: deep infiltrating endometriosis versus endometrioma only, deep infiltrating endometriosis versus adenomyosis only, and adenomyosis only versus endometrioma only. RESULTS: A total of 258 patients were included with 59 ovarian endometrioma only, 47 adenomyosis only, and 152 deep infiltrating endometrioses. Compared to endometrioma only, deep infiltrating endometriosis was associated with higher rates of severe dysmenorrhoea (odds ratio [OR] 2.80, 95% confidence interval [CI] 1.02-7.70) and out-of-pocket private surgical care (OR 4.72, 95% CI 1.85-12.04). Compared to adenomyosis only, deep infiltrating endometriosis was associated with a higher fertility desire (OR 13.47, 95% CI 1.01-180.59) and a lower body mass index (OR 0.89, 95% CI 0.79-0.99). In contrast, heavy menstrual bleeding was the hallmark of adenomyosis, being less common in patients with endometriosis. CONCLUSION: Deep infiltrating endometriosis is associated with severe dysmenorrhoea, pain related to urinary and gastrointestinal tracts, higher fertility desire and infertility rate. Patients with pain symptomatology and subfertility should be referred early to a tertiary centre with the capability to diagnose and manage deep infiltrating endometriosis.

Association of sarcopenia with important health conditions among community-dwelling Asian women.

This study aimed to examine sarcopenia prevalence using the Asian Working Group for Sarcopenia 2019 (AWGS) and the Foundation for the National Institutes of Health (FNIH) definitions, and their associations with important health conditions affecting midlife Singaporean women. Muscle mass and function were objectively assessed in 1201 healthy community-dwelling subjects aged 45-69 years under the Integrated Women's Health Program (IWHP). Dual-energy X-ray absorptiometry (DXA), handgrip strength and the Short Physical Performance Battery (SPPB) were measured, and the relationship between sarcopenia with hypertension, type 2 diabetes (T2DM), osteoporosis, depression/anxiety, and urinary incontinence were examined using binary logistic regression models. Sarcopenia prevalence was 18.0% and 7.7% by the AWGS and FNIH criteria respectively. Osteoporosis (aOR: 1.74, 95% CI: 1.02, 2.94) and T2DM (aOR: 1.98, 95% CI: 1.14, 3.42) was positively associated with AWGS- and FNIH-defined sarcopenia respectively, while hypertension was not, after adjustment for age, ethnicity, education levels and menopausal status. A negative percent agreement of 95.6% suggests good agreement between the criteria in the absence of sarcopenia. Even though they represent a single concept, sarcopenia by either criterion differed in their relationships with diabetes and osteoporosis, suggesting the need for further rationalization of diagnostic criteria.

Serum GDF9 and BMP15 as potential markers of ovarian function in women with and without polycystic ovary syndrome.

OBJECTIVE: Growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are critical paracrine regulators of female fertility and are predominantly expressed by oocytes. However, it is unknown if serum concentrations reflect changes in ovarian function and/or reproductive endocrine disorders. This study aimed to determine if serum GDF9/BMP15 are associated with ovarian, pituitary, oestrogenic, androgenic and metabolic characteristics and the ovarian pathologies, polycystic ovarian morphology (PCOM) and polycystic ovary syndrome (PCOS). DESIGN: Women aged 21-45 years (n = 381) were included from a cross-sectional study at the National University Hospital, Singapore. PATIENTS: Participants were volunteers and patients with possible PCOS. MEASUREMENTS: Anthropometric measurements, transvaginal ultrasound scans and serum sampling were performed and a questionnairecompleted. Serum GDF9 and BMP15 concentrations were matched with menstrual cycle length, ovarian protein and steroid hormone production, pituitary hormone production and metabolic assessments in women with PCOM or PCOS and those with neither (control). RESULTS: Serum GDF9 and BMP15 were detectable in 40% and 41% of women, respectively and were positively correlated with each other (r = 0.08, p = 0.003). GDF9, but not BMP15, was positively correlated with ovarian volume (p = 0.02) and antral follicle count (AFC) (p = 0.004), but not with anti-Müllerian hormone (p = 0.05). However, serum GDF9 and BMP15 concentrations were not significantly different between control, PCOM and PCOS women, nor associated with androgenic or metabolic PCOS features. However, the relationship between GDF9 and AFC differed between control, PCOM and PCOS women (p = 0.02). CONCLUSIONS: Serum GDF9 and BMP15 concentrations somewhat reflect ovarian but not androgenic or metabolic characteristics of PCOS, with increased GDF9 reflecting high AFC as seen in PCOM/PCOS.

Factors associated with poor sleep quality in midlife Singaporean women: The Integrated Women's Health program (IWHP).

Objective: To examine factors associated with poor sleep quality in community-dwelling midlife women. Methods: Healthy women (aged 45-69 years) of Chinese, Malay and Indian ethnicities attending well-women clinics at the National University Hospital, Singapore, completed the Pittsburgh Sleep Quality Index (PSQI). A PQSI score >5 denoted poor sleep quality. The women filled out validated questionnaires covering menopausal and genito-urinary symptoms, and mental health. Physical performance was measured. Bone mineral density and visceral adiposity were assessed by dual energy X-ray absorptiometry. Binary logistic regression analyses assessed independent factors for poor sleep. Results: Poor sleep quality was reported in 38.2% of women (n = 1094, mean age: 56.4 ± 6.2 years). Indian women had higher sleep disturbance scores than Chinese women (mean ± SD: 1.33 ± 0.58 vs 1.17 ± 0.49). Malays experienced more daytime dysfunction (0.54 ± 0.60 vs 0.33 ± 0.55) and had a higher overall PSQI score (6.00 ± 3.31 vs 5.02 ± 2.97) than the Chinese. A low education level (aOR: 1.76, 95% CI: 1.01-3.05), feelings of irritability (2.67, 1.56-4.60) and vaginal dryness (1.62, 1.03-2.54) were associated with poor sleep quality in the adjusted multivariable model. Women with moderate to severe disability were ∼3 times (2.99, 1.20-7.44) more likely to experience less than ideal sleep quality, while urinary incontinence (1.53, 1.08-2.17) and breast cancer history (2.77, 1.36-5.64) were also associates of poor sleep quality. Conclusion: Self-reports of education level, irritability, vaginal dryness, disability, urinary incontinence, and breast cancer history were independently related to poor sleep. Ethnic differences suggest the need for targeted interventions among the ethnic groups.

Polycystic ovary syndrome v.2023: Simplified diagnostic criteria for an East Asian phenotype.

Introduction: Two decades after the Rotterdam 2003 consensus workshop, there have been considerable advances in elucidating the pathophysiology and epidemiology of polycystic ovary syndrome (PCOS). This has prompted the re-examination of the features that characterise this common condition. Current definitions have led to great heterogeneity in the prevalence of PCOS and have contributed to inconsistent treatment protocols and assessment of therapeutic outcomes. Diagnosis is further complicated by the lack of universal agreement on threshold cut-offs for ovarian dysfunction and ethnic differences in hirsutism; both of which are key features in the definitions that are commonly used currently. These challenges often result in dissatisfaction with medical care among PCOS patients and their physicians. Method: Our factor analysis mathematically identified anti-Mullerian hormone (AMH), associated polycystic ovarian morphology (PCOM) and serum testosterone as the only significant cluster associated with menstrual cycle length variability. Results and Conclusion: As such, we propose a simplified criteria wherein the presence of at least 2 of the 3 features below would be sufficient to define PCOS: (1) chronic oligo-ovulation or anovulation as indicated by oligomenorrhea (cycle lengths >35 days) or amenorrhea; (2) PCOM: raised AMH ≥37.0 pmol/L instead of transvaginal ultrasound assessment of ovaries; and (3) Androgen excess, or raised serum androgens above the laboratory reference for women. Further studies are required to examine whether the proposed criteria would reduce diagnostic confusion and improve care and outcomes, especially among patients of East Asian ethnicities.

The Associations between Upper and Lower Body Muscle Strength and Diabetes among Midlife Women.

We hypothesized that a combined index of upper and lower body muscle strength would be more strongly associated with diabetes than either measure alone. Women recruited into the Integrated Women's Health Program had their handgrip strength (HGS) measured using a dynamometer and underwent a timed 5-repetition chair stand (RCS) test. HGS < 18 kg and RCS performance ≥ 12 s assessed upper and lower body strength, respectively, both individually and combined in a muscle strength index (MSI). Diabetes was defined as physician-diagnosed, use of anti-diabetic medication, or fasting blood glucose ≥ 7.0 mmol/L. Binary logistic regression examined the associations between muscle strength and diabetes. Of 1170 midlife women, 12.1% had diabetes. A low HGS was independently associated with diabetes (aOR: 1.59, 95% CI: 1.03, 2.44). Prolonged RCS was also associated with diabetes (aOR: 1.59, 95% CI: 1.09, 2.30), but this was not independent of visceral adiposity and muscle mass. A poor MSI had higher odds of diabetes (aOR: 2.37, 95% CI: 1.40, 4.03), independent of age, ethnicity, education level, menopausal status, smoking, alcohol consumption, physical activity, height, visceral adiposity, and muscle mass. The combination of both upper and lower body muscle strength into a composite MSI was more strongly associated with diabetes than either weak HGS or prolonged RCS alone in midlife women.

Diagnosis and management of polycystic ovary syndrome: Perspectives of clinicians in Singapore.

INTRODUCTION: To harmonise the diagnostic processes of polycystic ovary syndrome (PCOS) and enable clinicians to provide better patient care, it is critical to understand the knowledge gaps in PCOS diagnosis. We evaluated how clinicians in endocrinology, family medicine, general practice and gynaecology diagnose PCOS. METHODS: This cross-sectional survey involved 208 clinicians from specific subspecialties across various healthcare settings in Singapore. RESULTS: A total of 160 responses were included in the final analysis. Among all the diagnostic criteria, the Rotterdam 2003 criteria was most frequently used (66.3%). More than half of the gynaecologists reported having a standardised workplace protocol while the majority from other specialties reported otherwise. A large percentage of respondents (60.5%) were unable to identify the correct PCOS clinical features, which is concerning. Only 8.8% of respondents used clinical and biochemical hyperandrogenism, menstrual disturbances and pelvic ultrasound to diagnose PCOS without performing unnecessary and incorrect investigations. Most clinicians recognised insulin resistance/type 2 diabetes mellitus and fertility problems as complications while only a few recognised psychological complications. Many clinicians (37.3%) sought standardisation of PCOS diagnosis and management guidelines for improvement in PCOS care and 81.9% of respondents would appreciate standardised educational materials. CONCLUSION: This is the first study to the best of our knowledge that gives an insight into the diagnostic and management processes of PCOS among various healthcare institutions in Singapore. This study calls for greater harmonisation of diagnostic processes and holistic evidence-based management of patients with PCOS through standardised workplace protocols and patient education resources.

Sexual inactivity and sexual dysfunction in midlife Singaporean women: A prospective cross-sectional study of prevalence and risk factors.

OBJECTIVES: To examine factors relating to both sexual inactivity and sexual dysfunction in midlife Singaporean women. STUDY DESIGN: Sociodemographic, medical/lifestyle factors, physical activity, BMI, handgrip strength (HGS) and physical performance data collected from healthy Chinese, Indian, and Malay women, aged 45-69 years, attending gynaecology clinics. MAIN OUTCOME MEASURES: Sexual inactivity and sexual dysfunction (defined as total score ≤ 26.55) assessed using the Female Sexual Function Index (FSFI). RESULTS: 1048 women completed the FSFI. Mean (±SD) age was 56.2 (±6.2). Sexual inactivity was reported by 43.2% and was positively associated with older age [55-64 years (aOR 2.0, 95% CI 1.3-3.0) and ≥65 years (aOR 2.5, 95% CI 1.2-5.1)], younger menarche (aOR 1.8, 95% CI 1.3-2.5), lowest education (aOR 2.1, 95% CI 1.2-3.6), lowest income (aOR 1.8, 95% CI 1.1-2.8), unmarried (aOR 4.0, 95% CI 2.6-6.4), nulliparity (aOR 1.9, 95% CI 1.1-3.4), and BMI <18.5 kg/m2 (aOR 2.7, 95% CI 1.3-5.6). Among the sexually active, sexual dysfunction was identified in 70.3%. Sexual dysfunction was positively associated with menopause ≥10 years (aOR 2.4, 95% CI 1.1-5.0), nulliparity (aOR 3.0, 95% CI 1.1-9.8), moderate/severe vaginal dryness (aOR 13.8, 95% CI 4.8-38.7) and HGS <18 kg (aOR 1.9, 95% CI 1.1-3.2) and negatively associated with use of menopausal hormone therapy (aOR 0.3, 95% CI 0.1-0.6). CONCLUSION: This, the largest Singaporean sexual function study, is the first to include physical performance in a healthy population. Most were sexually active but reported dysfunction. Novel associations included underweight BMI with sexual inactivity and weaker HGS and Malay ethnicity with greater and less sexual dysfunction, respectively.

Randomized, double-blind, placebo-controlled trial to examine the safety, pharmacokinetics and effects of Epimedium prenylflavonoids, on bone specific alkaline phosphatase and the osteoclast adaptor protein TRAF6 in post-menopausal women.

BACKGROUND: Fragility fractures due to menopausal osteoporosis are a major cause of morbidity and mortality. Osteoporotic medications have substantial side effects that limit long term use. HYPOTHESES: Ingestion of a purified extract of Epimedium spp. (EP) is safe, can increase serum levels of prenylflavonoid metabolites, exert positive changes in bone specific alkaline phosphatase (BSAP), suppress of tumor necrosis factor receptor associated factor 6 (TRAF6) protein in osteoclast-precursor monocytes in peripheral blood and therefore have the potential to reduce post-menopausal bone loss. STUDY DESIGN & METHODS: Healthy postmenopausal women were randomized in a double-blind fashion to consume either EP prenylflavonoid extract (740 mg daily) or placebo daily for 6 weeks. The main outcome measures were safety and pharmacokinetics of EP flavonoids. Fasting blood was collected at 3- and 6-weeks, and two weeks after stopping medication for safety evaluations and measurement of BSAP. Peripheral blood monocytes were harvested for measurement of TRAF6 levels. Serum levels of the EP metabolites icariin, icariside I & II, icaritin and desmethylicaritin were measured using tandem mass spectrometry, and non-compartmental pharmacokinetic analyses performed using WinNonlin software. RESULTS: Between October 2018 and Jun 2020, 58 postmenopausal women, aged 57.9 ± 8.9 years, were randomized and completed the study. Consumption of EP prenylflavonoids was not associated with any significant adverse symptoms, with no changes in hepatic, hematological, and renal parameters observed. The main metabolites detected in sera after ingestion of EP prenylflavonoid capsules were desmethylicaritin, icaritin and icariside II. Icariin and icariside I were below detection levels. Ingestion of EP prenylflavonoids induced a median Cmax and AUC0→∞ for desmethylicaritin of 60.9 nM, and 157.9 nM ×day, respectively; and were associated with higher levels of BSAP (p < 0.05) and a trend (p = 0.068) towards lower levels of TRAF6 in peripheral blood monocytes eight weeks after commencing prenylflavonoid ingestion. Prenylflavonoid metabolites were not detected in the sera of placebo participants. CONCLUSIONS: Despite the widespread consumption of EP extracts, the safety, mechanisms of action of their bioactive compounds, and therapeutic indications in humans are unknown. Daily consumption of EP prenylflavonoids for six weeks was safe. The predominant metabolite in sera was desmethylicaritin. Rise in prenylflavonoid metabolites was associated with higher levels of the bone anabolic marker BSAP, suggesting potential therapeutic value for post-menopausal osteoporosis.

Higher risk of type 2 diabetes in women with hyperandrogenic polycystic ovary syndrome.

OBJECTIVE: To assess the risk of type 2 diabetes (T2D) in women with polycystic ovary syndrome (PCOS) in relation to body mass index (BMI) and the hyperandrogenic (HA) PCOS phenotype. DESIGN: Population-based cohort study. SETTING: Data from six Swedish national registers, with participants being followed for a maximum of 19 years. PATIENT(S): All women with an International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of PCOS, androgen excess, or anovulatory infertility born between 1950 and 1999 (n = 52,535) were identified in the Patient Register. The HA PCOS phenotype was defined by two filled prescriptions for anti-androgenic drugs. For each woman with PCOS, five control women (n = 254,624) were randomly chosen from the Total Population Register, matched for age and geographic area. INTERVENTION(S): No interventions were performed. MAIN OUTCOME MEASURE(S): International Statistical Classification of Diseases and Related Health Problems, version 10, diagnosis of T2D or prescription of antidiabetic treatment other than metformin. RESULT(S): The cumulative incidence rates of T2D were 1.3%, 4.4%, and 14.2% in controls (non-PCOS women) and women with normoandrogenic (NA) and HA PCOS, respectively. After adjustment for BMI, women with PCOS had a twofold higher rate of T2D than non-PCOS women (adjusted hazard ratio, 2.52 [95% confidence interval, 2.15-2.96]). Women with HA PCOS had a higher rate of T2D than those with NA PCOS (adjusted hazard ratio, 3.86 [95% confidence interval, 3.16-4.72]). CONCLUSION(S): Polycystic ovary syndrome is an independent risk factor for T2D, even after adjustment for BMI. Women with the HA PCOS phenotype face an even higher risk of T2D than those with the NA PCOS phenotype.

Menopausal osteoporosis: screening, prevention and treatment.

Screening for osteoporosis in women can be based on age and weight, using the Osteoporosis Screening Tool for Asians and assessment for other risk factors such as early menopause, Chinese ethnicity and other secondary factors. Based on the resulting risk profile, women can be triaged to dual-energy X-ray absorptiometry (DEXA) scanning for definite diagnosis of osteoporosis. Treatment should be considered in women with previous fragility fractures, DEXA-diagnosed osteoporosis and high risk of fracture. Exercise improves muscle function, can help prevent falls and has moderate effects on improvements in bone mass. Women should ensure adequate calcium intake and vitamin D. Menopausal hormone therapy (MHT) effectively prevents osteoporosis and fractures, and should be encouraged in those aged < 50 years. For women aged < 60 years, MHT or tibolone can be considered, especially if they have vasomotor or genitourinary symptoms. Risedronate or bisphosphonates may then be reserved for those aged over 60 years.

Effect of body mass index (BMI) on phenotypic features of polycystic ovary syndrome (PCOS) in Singapore women: a prospective cross-sectional study.

BACKGROUND: A diagnosis of Polycystic Ovary Syndrome (PCOS) and its related phenotypic features including increased hair growth can affect a woman's social and emotional well-being. We aim to determine firstly, if excess body weight affects menstrual cycle length, excessive hair growth and other phenotypic features in healthy women without PCOS and secondly, whether having PCOS exacerbates the effects of high body mass index (BMI). METHODS: A prospective cross-sectional study involving healthy women (21-45 years) recruited at an annual health screen for hospital staff and volunteers from the university community, and PCOS cases referred to tertiary gynecological clinics in Singapore. To dissect the independent and/or combinatorial effects of PCOS and BMI on the phenotypic features, subjects were divided into four categories: non-PCOS (normal BMI), non-PCOS (high BMI), PCOS (normal BMI), and PCOS (high BMI). General linear modelling was performed to compare clinical, ovarian, hormonal and metabolic parameters across these four categories. RESULTS: Of 389 participants, 134 (34.4%) were classified as PCOS and the remaining 255 (65.6%), as the non-PCOS population. Overall 45.2% of women had high BMI (≥ 23). Compared to non-PCOS subjects, women with PCOS had a higher BMI (mean (SD): 25.14 ± 6.46 vs 23.08 ± 4.36, p < 0.001). Women with PCOS and high BMI had increased hair growth with modified Ferriman-Gallwey (mFG) scores that were 2.96-fold higher versus healthy-normal BMI women (mean difference; 1.85, 95% CI 0.80-2.90). Compared to healthy-high BMI women, PCOS women with high BMI had significantly higher mean differences in mFG scores (1.79, 95% CI 0.64-2.93). In PCOS women, having high BMI also significantly increased mFG scores by 1.85-fold (mean difference; 1.82. 95% CI 0.52-3.12). This effect was mirrored by the additive effect of BMI and PCOS on free androgen index. No independent effect of high BMI on rates of oligomenorrhoea, antral follicle count, ovarian volume or serum androgens were observed. CONCLUSIONS: We observed an additive effect of body weight to increase hair growth in women with PCOS. Maximum mFG scores were present in PCOS women with high BMI. Such increases in mFG score may affect the self-esteem of women with PCOS.

A Smartphone App to Restore Optimal Weight (SPAROW) in Women With Recent Gestational Diabetes Mellitus: Randomized Controlled Trial.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes mellitus (T2DM). Lifestyle interventions aimed at postpartum weight loss to reduce T2DM risk have been reported, but poor compliance remains a barrier. Smartphone-based interventions may improve compliance, but data on its use in women with recent GDM are limited. OBJECTIVE: This trial aimed to investigate the efficacy of a smartphone app in restoring optimal weight following delivery in women with GDM, in the setting of a population with high rates of GDM and type 2 diabetes. METHODS: In this unblinded randomized controlled trial, 200 women with GDM were randomized to receive the intervention or standard care following delivery. The intervention enabled logging of weight, meals, and activity, with web-based interaction with a team comprising dieticians, a physiotherapist, and an occupational therapist. The primary outcome was an achievement of optimal weight (defined as the restoration of first trimester weight if first trimester BMI≤23 kg/m2 or weight loss of at least 5% from first trimester weight if first trimester BMI>23 kg/m2) at 4 months post partum. Secondary outcome measures included absolute weight loss, serum metabolic markers, self-reported nutritional intake, health education, and quality of life via questionnaires and user engagement in the intervention group. RESULTS: In total, 40% (38/96) of women in the intervention group achieved optimal weight at 4 months post delivery compared with 32% (28/93) in the control group (P=.27). Compared with the control group, women in the intervention group reported significantly reduced caloric intake at 4 months after delivery (P<.001) and higher health-directed behavior scores (P=.045). The intervention group also reported increased emotional distress scores (P=.01). At 4 months, participant engagement with the intervention was maintained at 60.8% (SD 33.9%). CONCLUSIONS: Although a statistically significant increase in women achieving healthy weight was not observed, this app remains promising, as women in the intervention group reported improved health behaviors and lower caloric intake. Importantly, the high retention rates suggest that a larger study with a longer follow-up period might confirm the effectiveness of this app for weight management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03324737; https://clinicaltrials.gov/ct2/show/NCT03324737. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-019-7691-3.

Predictors of circulating vitamin D levels in healthy mid-life Singaporean women.

Vitamin D levels were lowest in Indian and Malay compared to Chinese women, and in younger and employed women. The main reason for hypovitaminosis D in study women was deficient cutaneous production. Supplementation in regions with abundant sunshine should consider ethnicity and opportunities for exposure to sunlight. INTRODUCTION: Little is known about variations in circulating vitamin D levels in multiethnic mid-life women living in communities with year-round sunlight. Our study describes the circulating vitamin D levels and their sociodemographic predictors in mid-life Singaporean women. METHODS: Prospective cross-sectional study of healthy Singaporean women, age 45-69 years, who were not consuming vitamin D supplements. Total 25-hydroxyvitaminD [25(OH)D], the sum of 25(OH)D2 and 25(OH)D3, was measured by liquid chromatography-tandem mass spectrometry. RESULTS: The analytic cohort of 721 women, mean age 55.2±6.0 (±SD) years, was of Chinese (82%), Indian (11%), and Malay (7%) ethnicity. Their mean 25(OH)D level was 24.8±7.8ng/mL. One-third (32.6%) of the women had deficient 25(OH)D (≤20ng/mL) and 3.5% were severely deficient (<12ng/mL). 25(OH)D3 comprised 98% of the total circulating 25(OH)D level. Adjusted mean total 25(OH)D levels were significantly lower for women of Indian and Malay (vs Chinese) ethnicity, who were premenopausal or working outside the home. Indian and Malay women had higher odds (adjusted OR 5.58 (95% CI 3.22, 9.87) and 3.83 (95% CI 1.97, 7.57), respectively) of low 25(OH)D compared to Chinese women. Obesity was not an independent predictor of low 25(OH)D, as its strong crude association was confounded by ethnicity. The adjusted odds of low 25(OH)D was reduced in women ≥65 years (adjusted OR 0.37 (95% CI 0.14, 0.87)) compared to those aged 45-55 years. CONCLUSION: One-third of mid-life Singaporean women were 25(OH)D deficient, and the major independent predictors of deficiency were Indian or Malay ethnicity and younger age. Vitamin D supplementation in mid-life women should be targeted to those with documented deficiency or limited cutaneous production.

Preventing early-onset group B streptococcal sepsis: clinical risk factor-based screening or culture-based screening?

INTRODUCTION: Two strategies are available for prevention of early-onset group B streptococcal (GBS) sepsis - clinical risk factor-based screening and routine culture-based screening of pregnant women for GBS colonisation. In our hospital, we switched from the former to the latter approach in 2014. METHODS: We compared the incidence of early-onset GBS sepsis during 2001-2015 between infants born to pregnant women who were screened for GBS colonisation and those born to women who were not screened. RESULTS: Among 41,143 live births, there were nine cases of early-onset GBS sepsis. All infants with GBS sepsis were born to pregnant women who were not screened for GBS colonisation. The incidence of early-onset GBS sepsis among infants of women who were not screened was 0.41 per 1,000 live births (95% confidence interval [CI] 0.19-0.77) when compared to infants of women who were screened, for whom the sepsis incidence was zero per 1,000 live births (95% CI 0-0.19; p = 0.005). CONCLUSION: Our data suggests that routine culture-based screening of pregnant women for GBS colonisation is a better preventive strategy for early-onset GBS sepsis in neonates when compared to clinical risk factor-based screening.