Preconceptional maternal hyperandrogenism and metabolic syndrome risk in male offspring: a long-term population-based study.

PURPOSE: There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life. METHODS: Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20 years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons. RESULTS: There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18), P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1). CONCLUSION: The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring.

Correlation study between bone metabolic markers, bone mineral density, and sarcopenia.

OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.

Maternal androgen excess increases the risk of pre-diabetes mellitus in male offspring in later life: a long-term population-based follow-up study.

PURPOSE: Prenatal androgen exposure could be a source of early programming, leading to the development of cardiometabolic diseases in later life. In this study, we aimed to examine cardiometabolic disturbances in males exposed to maternal androgen excess during their prenatal life. METHODS: In this prospective population-based study, 409 male offspring with maternal hyperandrogenism (MHA), and 954 male offspring without MHA, as controls, were included. Both groups of male offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. Age-scaled unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between MHA with pre-diabetes mellitus (Pre-DM), type 2 diabetes mellitus (T2DM), pre-hypertension (Pre-HTN), hypertension (HTN), dyslipidemia, overweight, and obesity in the offspring of both groups. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05. RESULTS: A higher risk of Pre-DM (adjusted HR: 1.46 (1.20, 1.78)) was observed in male offspring with MHA after adjustment for potential confounders, including body mass index, education, and physical activity. However, no significant differences were observed in the risk of T2DM, Pre-HTN, HTN, dyslipidemia, overweight, and obesity in males with MHA compared to controls in both the unadjusted and adjusted models. CONCLUSION: Maternal androgen excess increases the risk of Pre-DM in male offspring in later life. More longitudinal studies with long enough follow-up are needed to clarify the effects of MHA on the cardiometabolic risk factors of male offspring in later life.

Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring: a long-term population-based follow-up study.

PURPOSE: Adverse intrauterine environment may predispose offspring to cardio-metabolic dysfunction in later life. In this study, we aimed to investigate the effects of maternal hyperandrogenism (MH) on cardio-metabolic risk factors in female offspring in later life. METHODS: This prospective population-based study included 211 female offspring with MH and 757 female offspring without MH (controls). Both groups were followed from baseline to the date of incidence of events, censoring, or end of the study period, whichever came first. Age scaled unadjusted and adjusted cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association of MH with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), overweight and obesity in offspring of both groups. Statistical analysis was performed using the software package STATA; significance level was set at P < 0.05. RESULTS: This study revealed a higher risk of T2DM (unadjusted HR 2.67, 95% CI 1.33-5.36) and overweight (unadjusted HR 1.41, 95% CI 1.06-1.88) in female offspring with MH, compared to controls. Results remained unchanged after adjustment for potential confounders including body mass index, education, physical activity, mother's age at delivery, birth weight, and childhood obesity. However, no significant difference was observed in the risk of pre-DM and obesity in females with MH, compared to controls in both unadjusted and adjusted models. CONCLUSION: This pioneer study with a long-term follow-up demonstrated that MH increases the risk of developing T2DM and being overweight in female offspring in later life. Further long-term population-based studies are needed to confirm these findings.

Aging and changes in adiposity indices: the impact of menopause.

PURPOSE: Aging is associated with significant changes in fat distribution and menopause may alter this process. This study aimed to investigate the longitudinal effect of menopause on changes in adiposity indices (AI). METHODS: A total number of 3876 non-menopausal women, aged > 20 years, who participated in the Tehran Lipid and Glucose study, were selected for the present study. They were followed from 1998 to 2018 at a 3-year interval and their adiposity indices were measured. Throughout the study, participants were categorized into two groups according to their menopausal status as group 1): women who reached menopause and group 2): women who did not reach menopause. The generalized estimation equation (GEE) models were used to compare the trend of changes in AIs between these two groups. RESULTS: At the end of the study, a total number of 1479 (38.2%) participants reached menopause. The odds of general obesity decreased by 5% (OR: 0.95, 95% CI: 0.90-0.99), and the odds of central obesity increased by 6% in group1 compared to group2 (OR: 1.06, 95% CI: 1.01-1.12). CONCLUSIONS: Menopause alters the impact of aging on central fat distribution. Increasing awareness of the related risk in menopausal women and their healthcare professional may prevent adverse related outcomes.

Effects of oral contraceptives on serum concentrations of adipokines and adiposity indices of women with polycystic ovary syndrome: a randomized controlled trial.

PURPOSE: To compare the effects of oral contraceptives (OCs) with different progestins, including Levonorgestrel (LNG), Desogestrel (DSG), Cyproterone Acetate (CPA), and Drospirenone (DRSP) on adipokines levels and adiposity indices in women with polycystic ovary syndrome (PCOS). METHODS: In this parallel randomized clinical trial, 120 women with PCOS randomly assigned to intervention with OCs containing LNG, DSG, CPA, or DRSP. Outcomes of interest, including serum concentrations of adiponectin, leptin, and resistin, and adiposity indices, i.e., body mass index (BMI), waist circumference (WC), obesity, central obesity, waist to hip ratio (WHR), waist to height ratio (WHtR), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), and visceral adiposity index (VAI), and lipid profiles were assessed at baseline, and 6 months of treatment. RESULTS: This study showed no significant differences in serum concentrations of adipokines between the four study groups after 6 months of treatment. Our results also showed that patients treated with various compounds of OC for 6 months had no significant differences in their adiposity indices, except for LAP (p = 0.04), and VAI (p = 0.03). PCOS patients treated with OCs containing CPA had significantly a higher mean LAP, compared to those using products containing LNG. Besides, patients treated with OCs containing CPA had significantly a higher mean VAI, compared to those treated with OCs containing DRSP. CONCLUSION: This study demonstrated that OCs with low androgenic and antiandrogenic activities had identical effects on serum concentrations of adipokines, and adiposity indices, except LAP, and VAI parameters. REGISTRATION NUMBER: IRCT20080929001281N3.

Shared motherhood IVF: high delivery rates in a large study of treatments for lesbian couples using partner-donated eggs.

Shared motherhood IVF treatment is becoming increasingly accepted among assisted reproductive techique practitioners and patients in Europe, although data on its overall efficiency remain scarce. This 6-year retrospective study from a single, private, UK HFEA-regulated centre included consecutive lesbian couples (n = 121) undergoing shared motherhood IVF treatment (141 cycles). Recipients were more parous and had undergone more previous intrauterine insemination and IVF treatments than donor partners, who had slightly higher ovarian reserve markers than recipients. Indications in most cycles (60%) were non-medical. Most (79%) egg-providers were stimulated with gonadotrophin releasing hormone antagonist protocol, and no moderate or severe cases of ovarian hyperstimulation syndrome (OHSS) arose. A total of 172 fresh and vitrified-warmed embryo transfers were carried out: 70% at the blastocyst-stage and 58% involved a single embryo. Cumulative live birth rate per receiver was 60% (72/120), and twin delivery rate was 14% (10/72). Perinatal outcome parameters were better for singleton than twin pregnancies, although the latter also achieved generally favourable outcomes. No significant difference in cumulative outcomes were found between synchronized and non-synchronized cycles. Shared motherhood IVF combines ovarian stimulation with single blastocyst transfer to provide a safe and effective treatment modality offering reassuring obstetrical and perinatal outcomes.

Prediction of age at menopause in women with polycystic ovary syndrome.

OBJECTIVE: Considering the role of anti-Müllerian hormone (AMH) in female fertility and its high levels in women with polycystic ovary syndrome (PCOS), the longer reproductive span of these women is in doubt. In the present study, we aimed to improve earlier predictions using a non-linear model to substantiate the question as to whether PCOS women reach menopause later. METHODS: In total, 1162 women aged 20-50 years, comprising 378 PCOS cases and 784 eumenorrheic non-hirsute women, met the eligibility criteria. A scatterplot matrix was drawn to detect the association between age and AMH; this association was explored using a fractional polynomial regression model. Model assumptions were checked by examining the distribution of the residuals and plotting the standardized residuals against the functional form of AMH. RESULTS: The serum concentration of AMH among PCOS participants was significantly higher than in the controls (5.4 ng/ml (IQR 2.8-9.1 ng/ml) vs. 1.4 ng/ml (IQR 0.6-2.7 ng/ml), p < 0.001). The estimated mean age at menopause was 51.4 (95% CI 45-59) years and 49.7 (95% CI 45-55) years in PCOS cases and healthy controls, respectively. CONCLUSIONS: These findings provide the insight that, as reflected through significantly higher average levels of AMH in PCOS women, their predicted reproductive lifespan could be 2 years longer than their normo-ovulatory counterparts.

NK cells control HIV-1 infection of macrophages through soluble factors and cellular contacts in the human decidua.

BACKGROUND: During the first trimester of pregnancy, HIV-1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV-1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV-1 infection. In this study, we investigate whether human decidual natural killer (dNK) cells control dM HIV-1 infection. RESULTS: Autologous cocultures of infected dMs with dNK cells reveal that dNK cells strongly inhibit dM HIV-1 infection. The addition of dNK cells to dMs at different times after infection suggests that the control occurs before the complete establishment of the infection. Double chamber cocultures show that cellular contacts are necessary for an optimal control of infection. Nevertheless, soluble factors secreted by dMs and dNK cells in double chamber cocultures partially inhibit dM HIV-1 infection, indicating that soluble factors have also a role in the control of infection. IFN-γ secretion is increased in infected and uninfected cocultures. We show that IFN-γ is involved in the control of dM HIV-1 infection by dNK cells. CONCLUSIONS: These results demonstrate that human dNK cells inhibit efficiently HIV-1 infection in dMs in vitro, and highlight the role of innate immune determinants in the control of HIV-1 transmission.

Non-cardiac comorbid health outcomes and prevalence after myocardial infarction: an umbrella review.

OBJECTIVE: There exists limited comprehensive evidence on the potential association between non-cardiac comorbidities and myocardial infarction (MI). Thus, we conducted an umbrella review of existing meta-analyses to provide a broad understanding of non-cardiac health outcomes associated with MI. MATERIALS AND METHODS: The primary focus on the prevalence of related health outcomes in patients with MI was systemically searched. Each original meta-analysis that was included had its methodological quality evaluated by a Measurement Tool Assessment Systematic Reviews 2 (AMSTAR2). To evaluate the certainty in the evidence for each outcome, we employed GRADE and the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The protocol was registered in PROSPERO (CRD42023458642). RESULTS: We identified seven meta-analyses comprising 126 studies with 336,581 participants from 22 countries and five continents. The pooled prevalence of comorbidities in patients with MI was 39% anxiety [95% confidence interval (CI), 30-48; GRADE, very low certainty], 29% depression (95% CI, 23-36; very low certainty), 39% frailty (95% CI, 24-55; very low certainty), and 23% failure of returning to work (95% CI, 16-29; very low certainty). The diagnosis of MI was associated with an increased risk of cognitive impairment (odds ratio, 1.45; 95% CI, 1.10-1.92; moderate certainty). Among frail patients, MI was associated with an increased risk of major bleeding (relative risk, 1.93; 95% CI, 1.08-3.45; low certainty) and mortality (relative risk, 2.29; 95% CI, 1.48-3.53; moderate certainty). However, we did not find any evidence of cancer risk associated with the development of MI. CONCLUSIONS: Our umbrella meta-analysis provided comprehensive evidence of the association between MI and several non-cardiac health conditions. The robustness of our study is attributed to the integration of evidence across several studies, thus, these insights offer valuable treatment options for policymakers and physicians to develop personalized health strategies.

National long-term trends in health-related quality of life using EQ-5D-3L in South Korea, 2008-2021, including the COVID-19 pandemic: a representative serial study of 2.8 million people.

OBJECTIVE: There is a scarcity of literature investigating the impact of the coronavirus disease 2019 (COVID-19) pandemic on long-term trends in health-related quality of life (HrQoL) using large-scale and representative data. Thus, we aimed to investigate the nationwide and long-term trends in quality of life (QoL) using the European Quality of Life- 5 dimensions, 3-level version (EQ-5D-3L) from a Korean representative serial study of 2.8 million people, 2008-2021. SUBJECTS AND METHODS: This Korean study used data on adults between 2008 and 2021 who participated in the Community Health Survey. Timeframes were categorized as COVID-19 mid-pandemic (2021) and pre-pandemic (2008-2019). The mean EQ-5D-3L index for the whole population and subgroups stratified by demographic characters was evaluated for each timeframe, and differences between before and during the COVID-19 pandemic were also analyzed. RESULTS: 2,827,240 adults who responded to the survey, 2008-2021, were eligible for this study. Overall EQ-5D index persistently decreased from 2008-2016, then minimally decreased during the pandemic, still being much higher than forecasted before the COVID-19 pandemic. The reduction in the rate of decline in QoL after the COVID-19 outbreak was especially marked in white-collared, young adults, people with 'good' or 'very good' subjective health, and college-educated or above group. On the other hand, the previously increasing trend of QoL in the elderly group has decelerated during the pandemic, and QoL of the 'very bad' subjective health group recorded the lowest in the whole study period. CONCLUSIONS: The present study investigated the long-term trend of QoL in Korean adults using serial data over the past 14 years, with a special emphasis on comparing the pre- and mid-COVID-19 pandemic periods.

Sex differences in the global burden of multidrug- resistant tuberculosis without extensive drug resistance in the general population and people living with HIV/AIDS, 1990-2019.

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.

Fluticasone nasal spray as an adjunct to Amoxicillin for acute sinusitis in children: a randomized controlled trial.

BACKGROUND: Approximately 0.5-2% of upper respiratory tract infections in adults and 6-13% of viral upper respiratory tract infections in children are complicated by acute sinusitis. This study was aimed to evaluate the coadministration effect of fluticasone nasal spray (FNS) with amoxicillin for AS in children. MATERIALS AND METHODS: One hundred children 2 to 14 years of age with acute sinusitis referred to Shahid Mohammadi Pediatric Hospital in Bandar Abbas were randomly allocated into two equal intervention and control groups to receive amoxicillin with fluticasone nasal spray one puff twice daily for 14 days and amoxicillin 80 to 100 mg/kg/ day for 14 days respectively. RESULTS: Twenty one (42%) of children in intervention group were cured completely and 2 (4%) children in control group had complete recovery (p < 0.001). Symptom severity score was 22.98 ± 2.95 before treatment that reduced to 13.26 ± 3.20 after treatment (p < 0.001). CONCLUSIONS: Use of fluticasone can reduce the severity of symptoms of sinusitis in children.

Association between sleep duration and diabetes mellitus: Isfahan Healthy Heart Program.

BACKGROUND: Recent studies revealed an association between sleep disturbance and metabolic disorders, such as obesity and metabolic syndrome. An aim of this study was to assess the relation between sleep duration and diabetes mellitus in a representative sample of the Iranian population. MATERIALS AND METHODS: Participants were 12514 individuals, (6123 men and 6391 women) studied in the baseline survey of a community based program entitled Isfahan healthy heart program (IHHP). Sleep time was obtained by validated questionnaire. Diabetes mellitus was defined as fasting glucose over 126 mg/dl or 2 hour post prandial glucose at glucose tolerance test over 200 mg/dl, or if the patient was on diabetic medication. The relation between the sleep time and diabetes was examined using categorical logistic regression with adjustment for sex, body mass index and waist circumference. RESULTS: Compared with those, sleeping 7-8 hours per night, the individuals with sleeping time of 5 hours or less and aged <60 years had an increased odd ratio for diabetes and an impaired glucose tolerance. (OR = 1.37 and 95% CI = 1.13, 1.67). CONCLUSION: Sleep duration of 5 hours or less in individuals under age 60 years is associated with an increased prevalence of diabetes mellitus and an impaired glucose tolerance test. This finding should be confirmed in longitudinal studies.

Assessing the endometrium: An update on current and potential novel biomarkers of receptivity.

A cyclical evolvement of the endometrium into a transient state of receptivity is crucial for acceptance of the semi-allogeneic foetus, conducive to pregnancy. Despite documentation of aberrances in this process within patients experiencing repeated embryo implantation failures and miscarriages, the endometrium is often overlooked in IVF clinics as the cause for failure. Focus instead is usually given to embryo-derived factors, such as aneuploidy. Nevertheless, failure of approximately 30 % of euploid embryos to implant demonstrates that other factors such as the endometrium require clinical exploration. Here, we review both traditional and novel methods used to assess endometrial receptivity such as identifying the WOI, endometrial immune profiling and transcriptomics panel testing. Where reported, we will also discuss their clinical application, as well as novel potential biomarkers within the pre-clinical research stages which show promise in their ability to assess endometrial receptivity.

Association between allergic rhinitis and despair, suicidal ideation, and suicide attempts in Korean adolescents: a nationally representative study of one million adolescents.

OBJECTIVE: There is a lack of studies establishing the association between allergic rhinitis (AR) and despair, suicidal thinking, and suicide attempts in adolescents and children at a population level. This study aimed to investigate whether there are associations between allergic rhinitis and despair, suicidal thinking, and suicide attempts. PATIENTS AND METHODS: The study utilized data from middle through high school adolescents from 2005-2021 who enrolled in the Korea Youth Risk Behavior Web-based Survey (KYRBS; 1,067,169). We assessed despair, suicidal thinking, and suicide attempts in the context of both non-atopic and atopic AR. Multivariable analysis was used to determine the association of variables. RESULTS: The prevalence of allergic rhinitis was 28.0%. 1,067,169 enrolled participants were included in the final analysis. There were 299,468 individuals with allergic rhinitis and 767,701 without. In the context of AR, adolescents were more likely to have despair [adjusted odds ratio (aOR), 1.16; 95% CI, 1.15-1.17], suicidal thoughts (aOR, 1.12; 95% CI, 1.11-1.13 for model 2), and suicide attempts (aOR, 1.13; 95% CI, 1.10-1.15 for model 2). Individuals with atopic AR were more likely in almost all measures to have despair, suicidal thinking, and suicide attempts than individuals with non-atopic AR. Females with AR were more likely to have suicide attempts and middle school students were more likely to have despair, suicidal thoughts, and suicide attempts. CONCLUSIONS: The results of this study warrant future studies investigating why AR is so closely associated with despair, suicidal ideation, and suicide attempts, with the goal of establishing suicide prevention strategies as well as improving overall mental health for adolescents.

National prevalence and determinants of COVID-19 vaccine hesitancy during the initial phase pandemic.

OBJECTIVE: Although previous studies have explored the causes of COVID-19 vaccine hesitancy during the pandemic, there is a lack of generality and reproducibility in these studies. Therefore, we aimed to comprehensively identify the determinants of COVID-19 vaccine hesitancy through a representative nationwide cross-sectional study conducted in South Korea. SUBJECTS AND METHODS: We used a nationwide, representative, and large-scale dataset from the 2021 Community Health Survey. By analyzing 193,495 participants, we investigated the nationwide incidence of COVID-19 vaccine hesitancy and the various causes thereof. RESULTS: The national prevalence of COVID-19 vaccine hesitancy was 5.7% (95% CI, 5.5-5.8). COVID-19 vaccine hesitancy was associated with an increased incidence of the following factors: (1) demographic factors including early-middle adulthood [vs. late; odds ratio (OR), 1.51; 95% CI, 1.38-1.65] and male sex (vs. female sex; OR, 1.08; 95% CI, 1.01-1.14); (2) physically healthy subjects; (3) lower socio-economic status (vs. high household income; OR, 1.28; 95% CI, 1.19-1.38); (4) having mental illness (vs. normal mental status; OR, 1.25; 95% CI, 1.13-1.38); and (5) unhealthy habits such as current smoking (vs. non-smoking; OR, 1.22; 95% CI, 1.13-1.31); and insufficient physical activity (vs. sufficient; OR, 1.08; 95% CI, 1.01-1.17). Common reasons for vaccine hesitancy were concerns about side effects (41.34%), health problems (24.60%), and inability to select the type of vaccine (14.13%). CONCLUSIONS: This representative large-scale nationwide study conducted in South Korea investigated the nationwide prevalence and determinants of vaccine hesitancy. Our results provide useful public health information, especially on novel aspects of vaccination strategies, for policymakers to improve the acceptance of COVID-19 vaccines.