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.

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.

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.

Blood pressure and adiposity in midlife Singaporean women.

Hypertension is a major risk factor for cardiac events and stroke. Visceral adipose tissue (VAT) is known to increase the risk of incident hypertension in adults. Although adiposity has been linked to markers of inflammation, few studies have examined these markers as potential mediators of the association between visceral adiposity and elevated blood pressure. We evaluated sociodemographic, reproductive, and lifestyle risk factors for elevated blood pressure among midlife Singaporean women. A total of 1189 women, with a mean age of 56.3 ± 6.2 years, from the Integrated Women's Health Program (IWHP) at National University Hospital, Singapore were studied. Hypothesized risk factors and levels of inflammatory markers were examined in relation to systolic blood pressure (SBP) and diastolic blood pressure (DBP) using multivariable linear regression models. Prehypertension (SBP 120-139 mmHg and/or DBP 80-89 mmHg) and hypertension (SBP ≥140 mmHg and/or DBP ≥90 mmHg) were observed in 518 (43.6%) and 313 (26.3%) women, respectively. Compared to women in the lowest tertiles, women in the middle and upper tertiles of VAT had 7.1 (95% CI, 4.4, 9.8) mmHg and 10.2 (95% CI, 6.7, 13.7) mmHg higher adjusted SBP, respectively. Nulliparous older women with a lower education level and those with no or mild hot flashes also had a significantly higher adjusted SBP. No significant independent risk factors were observed for DBP. Adjustments for IL-6, TNF-α, and hs-CRP did not attenuate the association between VAT and SBP. In summary, we found an independent positive association between VAT and SBP. Elevated levels of inflammatory markers did not mediate the increase in SBP in women with high VAT.

Comparison of the Osteoporosis Self-Assessment Tool for Asians and the fracture risk assessment tool - FRAX to identify densitometric defined osteoporosis: A discriminatory value analysis in a multi-ethnic female population in Southeast Asia.

OBJECTIVES: The accuracy of FRAX® as a screening tool to identify osteoporosis and how it compares with tools such as Osteoporosis Self-Assessment Tool for Asians (OSTA), in Southeast Asian women has so far been unexplored. We aimed to determine the FRAX® thresholds that accurately identify densitometric osteoporosis and to compare its performance with that of OSTA for this purpose. METHODS: Singaporean postmenopausal women (n = 1056) were evaluated. FRAX® Major Osteoporotic Fracture Probability (MOFP), Hip Fracture Probability (HFP) scores, and OSTA indices were calculated. Receiver operating characteristic (ROC) curves were constructed and via the Youden index, the optimal cut-off points of balanced sensitivity and specificity for dual energy X-ray absorptiometry (DXA)-defined osteoporosis were identified and the performance characteristics were compared. RESULTS: A FRAX® MOFP threshold of ≥3.7% had sensitivity, specificity, positive predictive value and negative predictive value of 0.78 (0.73-0.83), 0.63 (0.59-0.66), 0.4 (0.36-0.44), and 0.9 (0.87-0.92), respectively in identifying osteoporosis. The corresponding values for a HFP threshold of ≥0.6% were 0.85 (0.80-0.89), 0.58 (0.55-0.62), 0.39 (0.35-0.43), and 0.92 (0.9-0.94) and that for an OSTA index cut-off of ≤ -1.2 were 0.76 (0.70-0.81), 0.74 (0.71-0.77), 0.48 (0.43-0.54), and 0.91 (0.88-0.93). The area under the ROC curves were 82.8% (79.9%-85.6%), 77.6% (74.2%-81%), and 79.6% (76.5%-82.8%) for OSTA, MOFP, and HFP thresholds respectively. CONCLUSIONS: FRAX® and OSTA perform comparably in identifying osteoporosis in our population. OSTA has only 2 parameters and may be simpler to use. However, FRAX® may also have a role in primary screening to identify the postmenopausal woman to be referred for DXA scanning and may help facilitate fracture risk reduction discussions with the patient.

Risk factors for insulin resistance in midlife Singaporean women.

OBJECTIVES: To understand the extent to which risk factors for insulin resistance are mediated by body mass index (BMI), visceral adipose tissue (VAT), physical activity and performance, and the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)- α, and high-sensitivity C-reactive protein (hs-CRP). STUDY DESIGN: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF- α, and hs-CRP were measured. MAIN OUTCOME MEASURE: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF- α (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF- α, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66). CONCLUSIONS: Insulin resistance was independently associated with obesity, high VAT, low physical performance, and high levels of TNF- α in midlife Singaporean women. These variables entirely explained the significant differences in insulin resistance between women of Chinese, Malay and Indian ethnicity.

Risk factors and prevalence of urinary incontinence in mid-life Singaporean women: the Integrated Women's Health Program.

INTRODUCTION AND HYPOTHESIS: The objective was to identify the prevalence and risk factors for urinary incontinence (UI) in healthy midlife Singaporean women. METHODS: Healthy women, aged 45-69 years, were assessed for UI and sociodemographic characteristics, including ethnicity, menopausal status, parity, and body mass index (BMI). UI subtypes corresponding to stress (SUI) alone, urge (UUI) alone, mixed (MUI), and leakage (drops only) incontinence were classified using the Urinary Distress Inventory 6 (UDI-6). Risk factors were examined using Chi-squared tests, followed by sequential multivariate logistic regression to estimate adjusted odds ratios (aOR and 95% confidence intervals). RESULTS: A total of 1,119 women (mean age 56.2 ± 5.2) completed the UDI-6. 52.3% reported any UI; MUI and SUI were the most common, each affecting 20% of women. Post-menopausal women had a lower risk (aOR 0.5 [0.3-0.9]) of SUI, but a higher risk (aOR 4.4 [1.0-19.9]) of UUI compared with premenopausal women. Higher education was negatively associated (aOR 0.3 [0.2-0.7]) with UUI, but positively associated with MUI (aOR 2.3 [1.3-4.0]). Parity (1-2 children) increased the risk of SUI (aOR 1.8 [1.0-3.1]), but reduced the risk of UUI (aOR 0.4 [0.2-0.9]). Obesity was associated with increased risk for MUI (aOR 2.2 [1.4-3.4]) and leakage (aOR 2.0 [1.0-4.1]). Malays and Indians had a higher risk of MUI, having (aOR 2.1 (1.2-3.7) and 1.7 (1.1-2.7) respectively compared with Chinese, a difference mediated by higher BMI. CONCLUSION: Urinary incontinence is a major morbidity prevalent in healthy midlife Asian women. Post-menopausal status, education level, parity, BMI (and its link with ethnicity) are independent risk factors in this population, and should be incorporated into counseling and targeted interventions.

Ethnic differences in bone mineral density among midlife women in a multi-ethnic Southeast Asian cohort.

Chinese Singaporean middle-aged women have significantly lower femoral neck bone mineral density and higher lumbar spine bone mineral density than Malays and Indians, after adjustment for age, body mass index, and height. PURPOSE: Information regarding mediators of differences in bone mineral density (BMD) among Asian ethnicities are limited. Since the majority of hip fractures are predicted to be from Asia, differences in BMD in Asian ethnicities require further exploration. We compared BMD among the Chinese, Malay, or Indian ethnicities in Singapore, aiming to identify potential mediators for the observed differences. METHODS: BMD of 1201 women aged 45-69 years was measured by dual-energy X-ray absorptiometry. We examined the associations between ethnicity and BMD at both sites, before and after adjusting for potential mediators measured using standardized questionnaires and validated performance tests. RESULTS: Chinese women had significantly lower femoral neck BMD than Malay and Indian women. Of the more than 20 variables examined, age, body mass index, and height accounted for almost all the observed ethnic differences in femoral neck BMD between Chinese and Malays. However, Indian women still retained 0.047 g/cm2 (95% CI, 0.024, 0.071) higher femoral neck BMD after adjustment, suggesting that additional factors may contribute to the increased BMD in Indians. Although no crude ethnic differences in lumbar spine BMD were observed, adjusted regression model unmasked ethnic differences, wherein Chinese women had 0.061(95% CI, - 0.095, 0.026) and 0.065 (95% CI, - 0.091, 0.038) g/cm2 higher lumbar spine BMD compared to Malay and Indian women, respectively. CONCLUSION: BMD in middle-aged Asian women differ by ethnicity and site. Particular attention should be paid to underweight women of Chinese ethnic origin, who may be at highest risk of osteoporosis at the femoral neck and hence hip fractures.

Sleep apnea and femoral neck BMD among Singaporean mid-life women.

The relationship between sleep apnea and bone health remains controversial. This study explored the relationship between sleep apnea and femoral neck BMD in midlife Asian women. Partner-witnessed apnea predicted higher femoral neck BMD, an effect validated by the STOP index. Our findings suggest that sleep apnea may protect bone health. PURPOSE: The menopause transition is associated with decline in bone mineral density (BMD) and sleep quality. However, any relationship between these two factors remains controversial. This study explored the association between sleep apnea and femoral neck BMD in middle-aged women. METHODS: Participants (n = 1201) aged 45-69 years attending well-women visits at the National University Hospital, Singapore were recruited. Self-reported breathing discomfort and snoring, partner-witnessed apnea and snoring were assessed from the Pittsburgh Sleep Quality Index. Femoral neck BMD was assessed with dual-energy X-ray absorptiometry scan and classified into tertiles based on T-scores. Factors reported to affect sleep apnea and bone health in medical literature were potential covariates, p < 0.10. Multivariable ordinal regression analyses assessed associations between sleep measures and BMD. To further validate our findings, we analyzed four sleep apnea characteristics from the STOP questionnaire, a screening tool for sleep apnea. All analyses were performed using SPSS version 20.0. RESULTS: Mean (SD) age of participants was 56.3 (6.2) years. Partner-witnessed apnea predicted higher BMD tertiles (OR per unit increase in severity 1.39, 95% CI [1.02, 1.89]), independent of age, ethnicity, diabetes, BMI, and handgrip strength. This was further corroborated by the STOP index (OR 1.45, 95% CI [1.07, 1.96]). CONCLUSIONS: This study adds to the literature on sleep apnea and bone health in a non-Caucasian and younger population. Our findings support OSA-associated intermittent hypoxia protecting bone health.