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STUDY QUESTION Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION Our findings were specific to Han Taiwanese individuals, with genetic correlation analyses conducted in East Asians. Further research in other ethnic groups is necessary. WIDER IMPLICATIONS OF THE FINDINGS Our study provides insights into the genetic architecture of AAM and its health-related outcomes in East Asians, highlighting causal links between BMI/T2D and earlier AAM, which may suggest potential prevention strategies for early puberty. STUDY FUNDING/COMPETING INTEREST(S) The work was supported by China Medical University, Taiwan (CMU110-S-17, CMU110-S-24, CMU110-MF-49, CMU111-SR-158, CMU111-MF-105, CMU111-MF-21, CMU111-S-35, CMU112-SR-30, and CMU112-MF-101), the China Medical University Hospital, Taiwan (DMR-111-062, DMR-111-153, DMR-112-042, DMR-113-038, and DMR-113-103), and the Ministry of Science and Technology, Taiwan (MOST 111-2314-B-039-063-MY3, MOST 111-2314-B-039-064-MY3, MOST 111-2410-H-039-002-MY3, and NSTC 112-2813-C-039-036-B). The funders had no influence on the data collection, analyses, or conclusions of the study. No conflict of interests to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Background: Pelvic inflammatory disease (PID) is an important health issue for women. Infection and inflammation play an important role in carcinogenesis and PID has been reported to be associated with ovarian cancer in some small scale studies.Aim: We sought to determine whether PID is associated with an elevated risk of ovarian cancer in Asian women.Methods: Using data from Taiwan's National Health Insurance Research Database (NHIRD), our retrospective cohort study included women diagnosed with PID (cases) between the years of 2000 till 2012. Each case was matched with two women without PID (controls) by age and the year of first entry into the database. Both study cohorts were followed-up until the first event of ovarian cancer, withdrawal from the NHI program, death, or the end of the study period (December 31, 2012). Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios (HRs and aHRs) with their corresponding 95% confidence intervals (95% CIs) for the association of PID and ovarian cancer risk, with and without adjusting for potential confounders.Results: During an approximate 10 years of follow-up, cases were significantly more likely than controls to develop ovarian cancer (incidence rates of 0.27 and 0.16 per 1,000 person-years, respectively; P < 0.001). Women with a history of PID had a 1.49-fold elevated risk for ovarian cancer (aHR, 1.49; 95% CI, 1.21-1.84; P < 0.001).Conclusion: Our study evidence supports the contention that PID increases the risk of developing ovarian cancer among Taiwanese women. Gynecologists should undertake careful assessments and closely follow patients with PID, who are at long-term risk of developing ovarian cancer. Our findings need further verification in other international cohorts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between hormone replacement therapy (HRT) and the risk of bone fracture in menopausal women in Taiwan.Study Design: The longitudinal, population-based, nested case-control study in Taiwan involved 5269 women aged > 45 years with fractures and 21,076 matched randomly selected controls without fractures. A conditional logistic regression model of analysis was employed.Main Outcome Measures: The association between the risk of bone fracture and various HRT-related parameters, including the timing, dosage, and adherence, was investigated.Results: Women with menopausal syndrome were protected from fractures when they received hormone drugs at high cumulative defined daily doses (DDDs) (Cumulative DDDs≥360) (odds ratio [OR]: 0.90, 95 % confidence interval [CI]: 0.82-0.99) and when their adherence was high (over 0.5) (OR: 0.70, 95 % CI: 0.60-0.82). The risk of fracture also decreased with high cumulative DDDs and high adherence combined (OR: 0.71, 95 % CI: 058-0.86). Subgroup analyses suggested that estrogen-containing regimens showed a protective effect against fractures at high cumulative DDDs or when adherence was high. Similar results were also observed with progestogen-containing regimens. Past exposure to an estrogen-containing regimen showed a protective effect against fractures when adherence was high. Past exposure to a progestogen-containing regimen showed a protective effect against fractures at high cumulative DDDs and when adherence was high.Conclusions: The results indicate that past exposure to estrogen-containing or progestogen-containing regimens exerts protective effects against bone fracture. These effects increased with higher cumulative DDDs and with adherence in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

• The definition for slowness and weakness were adjusted to the current criteria produced in 2019. • The data about frail population was analyzed in the revised manuscript, as well as the prevalence about the each index of Fried criteria. • The method for multivariate regression analysis was described in detail. • For the relationship about cognitive function, frailty and PF and mortality, more discussion was shown. Both frailty and prefrailty (PF) are related to mortality. However, there is no consensus about the PF subtypes for prediction of the mortality risk. We aimed to compare the 5-year mortality of functionally independent geriatric outpatients with nonfrailty, different PF subtypes and frailty. This was a single-center, retrospective cohort study. Community-dwelling older adults who visited the geriatric outpatient clinic in a healthcare institution in Taiwan were enrolled. PF1 was defined based on exhaustion and/or body weight loss whereas PF2 was defined by one or two of the following criteria: weakness, slowness, and low physical activity. Frailty was defined by three or more above criteria. Demographics and results of comprehensive geriatric assessment were compared and Kaplan–Meier survival analysis was used to determine the 5-year survival among the nonfrail, PF1, PF2 and frail groups. Of the 982 participants, the proportion of PF and frailty was high (PF 45.7% and frailty 24.5%). The cumulative 5-year survival rate of the nonfrail group, PF1, PF2 subgroups and frail group was 98.6%, 95.8%, 89.1% and 81.3% respectively. Age, male sex, PF2 subtype and frailty were significantly associated with 5-year mortality [hazard ratio (95% confidence interval) 1.05 (1.01–1.08), 1.96 (1.08–3.57), 5.18 (1.57–17.09), and 6.87 (2.05–23.04), respectively]. The proportion of PF and frailty was high in old outpatient population with functional independence. PF2 subtypes and frailty could influence the 5-year mortality risk in these participants. Identifying PF2 participants earlier and instituting prompt intervention may be beneficial in older patients. [ABSTRACT FROM AUTHOR]

Abstract: Circulating levels of inflammatory and prothrombotic factors are elevated in the metabolic syndrome (MS) and linked with the occurrence of cardiovascular events. The aim of our study was to investigate the relationship between inflammatory and prothrombotic markers and the MS in elderly institutionalized residents. A total of 326 non-diabetic residents of Chuang-Hua Veterans Care Home (age: 79.9±4.1 years; 100% males) were enrolled. MS was diagnosed according to the AHA/NHLBI Scientific Statement criteria. Body fat percentage was measured by bioelectrical impedance analysis. Insulin resistance was calculated by homeostasis model assessment for insulin resistance (HOMA-IR). Inflammatory markers, including tumor necrosis factor-a (TNF-α), high sensitivity C-reactive protein (hsCRP), and plasminogen activator inhibitor-1 (PAI-1), were determined using ELISA. Elderly residents with the MS had higher systolic and diastolic blood pressures (both p < 0.001) and higher HOMA-IR (p < 0.001), hsCRP (p = 0.008), and PAI-1 levels (p < 0.001) than those without the MS. On multivariate logistic regression analysis, PAI-1 was an independent risk factor for the MS. Of the MS components, elderly residents with higher waist circumferences and higher levels of plasma fasting glucose, and triglyceride (TG), and lower levels of high density lipoprotein (HDL) had higher PAI-1 levels than those without the above components. [Copyright &y& Elsevier]

Objective: To investigate the genetic characteristics of idiopathic centr al precocious puberty (ICPP) and validate its polygenic risk for early puberty. Design and methods: A bootstrap subsampling and genome-wide association study were performed on Taiwanese Han Chinese girls comprising 321 ICPP patients and 148 controls. Using previous GWAS data on pubertal timing, a replication study was performed. A validation group was also in vestigated for the weighted polygenic risk score (wPRS) of the risk of early puberty. Results: A total of 105 SNPs for the risk of ICPP were identified, of whi ch 22 yielded an area under the receiver operating characteristic curve of 0.713 for the risk of early p uberty in the validation group. A replication study showed that 33 SNPs from previous GWAS data of pubertal timing were as sociated with the risk of ICPP (training group: P-value < 0.05). In the validation group, a cumulative effect was observe d between the wPRS and the risk of early puberty in a dose-dependent manner (validation group: Cochran-Armitage trend test: P-value < 1.00E-04; wPRS quartile 2 (Q2) (odds ratio (OR) = 5.00, 95% CI: 1.55-16.16), and wPRS Q3 (OR = 11.67, 95% CI: 2.44-55.83)). Conclusions: This study reveals the ICPP genetic characteristics with 22 in dependent and 33 reported SNPs in the Han Chinese population from Taiwan. This study may contribute to understand the genetic features and underlying biological pathways that control pubertal timing and pathogenes is of ICPP and also to the identification of individuals with a potential genetic risk of early puberty. [ABSTRACT FROM AUTHOR]

Objective: Evidence for an association between uterine leiomyoma and increased risk of endometriosis is limited by small sample sizes and short follow-up periods. We assessed this association in a large nationwide sample with 14 years of data. Design: Data were sourced from Taiwan's Longitudinal Health Insurance Database 2000 (LHID2000). Materials and methods: We identified 31,239 women aged ≥20 years diagnosed with uterine leiomyoma (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] code 218) between Jan 1, 2000 and Dec 31, 2012, who were matched with 124,956 controls (1:4) by 5-year age groups and year of diagnosis. Follow-up was from the date of LHID2000 entry to the first occurrence of endometriosis, loss to follow-up, insurance termination, or until December 31, 2013, whichever was earlier. Results: In Cox regression analysis, the adjusted hazard ratio (aHR) for endometriosis in women with uterine leiomyoma was 6.44 (95% CI, 6.18, 6.72) compared with controls. The risk of endometriosis was significantly increased in women with uterine leiomyoma and comorbidities of tube-ovarian infection (aHR 2.86; 95% CI, 1.28, 6.36), endometritis (1.14; 1.06, 1.24), infertility (1.26; 1.16, 1.37), or allergic diseases (1.11; 1.05, 1.17). Having both uterine leiomyoma and endometritis significantly increased the risk of endometriosis (aHR 6.73; 95% CI, 6.07, 7.45) versus having only uterine leiomyoma (6.61; 6.33, 6.91) or endometritis (1.49; 1.31, 1.69). Similarly, having both uterine leiomyoma and infertility significantly increased the risk of endometriosis (aHR 6.95; 95% CI, 6.21, 7.78) versus having only uterine leiomyoma (6.66; 6.38, 6.96) or infertility (1.78; 1.57, 2.02). Conclusions: A diagnosis of uterine leiomyoma appears to increase the risk of endometriosis. Patients presenting with uterine fibroids should be encouraged to give informed consent for possible simultaneous surgical treatment of endometriosis. [ABSTRACT FROM AUTHOR]

Background: The incidence of female stroke has increased gradually and has begun occurring at a younger age in recent years. Given that women live longer than men, stroke would cause more negative and longer-term impacts on the rest of the lives of women. There are few related studies on Asian women. We aimed to evaluate stroke risk in Asian women following hypertensive pregnancy disorders.Methods: Using the Taiwan National Health Insurance database, we designed a retrospective study that included pregnant women between 2000 and 2013. We selected an age-matched control group of women without hypertensive pregnancy disorders at a 1:3 ratio. The endpoint was any episode of stroke; otherwise, the patients were tracked until December 31, 2013. After the index date until the end of 2013, Cox proportional hazards analysis was used to compare the risk of incident stroke. The risk factors for stroke were determined using Cox proportional regression to calculate the hazard ratio (HR) compared with the control group.Results: During the follow-up period, the Kaplan-Meier analysis indicated that patients with hypertensive pregnancy disorders had a significantly higher risk of developing stroke than did patients without hypertensive pregnancy disorders (log-rank test P < 0.001). Multivariate Cox regression analysis demonstrated that the case group had a 2.134-fold increased risk of stroke (HR = 2.134; 95% CI = 1.817-2.505; P < 0.001).Conclusion: Our study provided evidence of an increased risk of stroke in patients with hypertensive pregnancy disorders. Compared with those without such disorders, the patients who had experienced the disorders had a 2.134-fold (P < 0.001) higher risk of developing stroke in the future. [ABSTRACT FROM AUTHOR]

Background: Dysmenorrhea and stroke are health problems affecting women worldwide in their day-to-day lives; however, there is limited knowledge of the stroke risk in women with dysmenorrhea, and there have been no studies assessing the specific distribution of stroke subtypes. This case-control study assessed stroke subtypes by age and the role of comorbidities in women with dysmenorrhea. Methods and findings: Data obtained between 1997 and 2013 from Taiwan's health insurance database identified 514 stroke cases and 31,201 non-stroke controls in women with dysmenorrhea aged 15–49 years. Proportional distributions of subtypes and odds ratios (ORs) of stroke associated with comorbidities by age and subtype were measured. We found that the stroke risk in dysmenorrheal patients increased with age, and that hypertension was nine-fold more prevalent in the stroke cases than in the controls and was associated with an adjusted OR of 4.53 (95% confidence interval (CI) = 3.46–5.92) for all stroke cases. Moreover, the proportion of hemorrhagic stroke was greater than that of ischemic stroke in younger dysmenorrheal patients between 15–24 years old (50.5% vs. 11.4%), whereas this was reversed in those aged 30–49 years old (16.1% vs. 21.0%). Overall, 25.3% of the stroke cases consisted of transient cerebral ischemia and 31.3% were other acute but ill-defined cerebrovascular diseases, in which the prevalence increased with age for both types of strokes. Hypertension was the comorbidity with the highest OR associated with each subtype stroke; diabetes, hyperlipidemia, arrhythmia, and thyroid disease were also comorbidities that were significantly associated with ill-defined cerebrovascular diseases. Conclusions: The stroke type varies by age in dysmenorrheal patients, and hypertension is the most important comorbidity associated with all types of stroke; therefore, more attention for stroke prevention must be paid to women with dysmenorrhea, particularly when combined with comorbidities. [ABSTRACT FROM AUTHOR]

Background: Pelvic inflammatory disease (PID) is an infectious disease that causes tubal occlusion and other pelvic and abdominal adhesions. The incidence of pelvic inflammatory disease (PID) has increased due to the sexually active status of the young population. This leads to a more serious problem and a larger effect than previously observed. However, there have been few studies on this topic in Asian populations. Aim: We aimed to evaluate the risk of preterm labor and/or ectopic pregnancy in Taiwanese women following PID. Design: Using the Taiwan National Health Insurance Database, we designed a retrospective cohort study that included 12- to 55-year-old pregnant women between 2000 and 2010. We selected a 1:3 age-matched control group of non-PID women. The endpoint was any episode of preterm labor or ectopic pregnancy; otherwise, the patients were tracked until 31 December 2010. Methods: The risk factors for preterm labor or ectopic pregnancy were explored. For cases included from the index date until the end of 2010, we analyzed the risk of incident preterm labor or ectopic pregnancy. With the use of a multivariate Cox proportional hazard regression analysis, we calculated the hazard ratio (HR) with a 95% CI and compared it with that of the control group. Results: This study examined 30,450 patients with PID and 91,350 controls. During the follow-up period, patients in the PID group were more likely to develop preterm labor or ectopic pregnancy than patients in the control group. The cumulative incidence rates for developing preterm labor were 1.84% (561/30,450 individuals) in patients with PID and 1.63% (1492/91,350 individuals) in patients without PID. On the other hand, the cumulative incidence rate for developing ectopic pregnancy in patients with PID was 0.05% (14/30,450 individuals) but was only 0.04% (33/91,350 individuals) in patients without PID. Compared with those without PID, the patients with PID had a 1.864 times (P<0.001) higher risk of developing preterm labor and a 2.121 times (P = 0.003) higher risk of developing ectopic pregnancy. Conclusion: Our study provided evidence of an increased risk of preterm labor or ectopic pregnancy in PID patients. [ABSTRACT FROM AUTHOR]

Massive postpartum hemorrhage is one of the major complications in the peripartum period. In some critical cases, hemostasis is hard to achieve even after a hysterectomy has been performed. Recombinant activated factor VII has been reported as a promising adjuvant therapy for obstetric hemorrhage, although it remains unlicensed for this indication. Eight cases receiving recombinant activated factor VII in postpartum hemorrhage refractory to the conventional therapy in a Taiwanese hospital were analyzed retrospectively. A good response, defined as bleeding control in 15 min, was achieved in six patients (75%) with a single dose ranging from 55 to 105 mg/kg. The two patients with a poor response were later discovered to have had unsolved birth canal injuries. No drug-related adverse effects were noted. We recommend that any surgical bleeding should first be controlled, as well as the correction of metabolic and hematological abnormalities; however, in the situation of intractable postpartum hemorrhage, recombinant activated factor VII offers a salvage therapy and should be considered early, even before hysterectomy. [ABSTRACT FROM AUTHOR]