Natto intake is a risk factor of Bacillus subtilis bacteremia among children undergoing chemotherapy for childhood cancer: A case-control study.

BACKGROUND: Natto, a popular, daily food in Japan, is made from soybeans fermented by Bacillus subtilis. The aim of this retrospective case-control study (matched 1: 4) is to determine whether natto intake is a risk factor of B. subtilis bacteremia in this population. METHODS: The retrospective, matched case-control study was conducted at Tokyo Metropolitan Children's Medical Center between April 2012 and June 2020 and included pediatric patients younger than 15 years who received chemotherapy for cancer. Patients who received hematopoietic stem cell transplantation were excluded. Patients with B. subtilis bacteremia were compared with controls matched for age and underlying diseases. Dietary information within seven days from the date of blood culture collection was extracted from medical records. Multivariate logistic regression was performed to define the risk factors of B. subtilis bacteremia. RESULTS: In total, 23 patients with B. subtilis bacteremia were identified and matched to 92 controls. The percentage of patients and controls who ingested natto within seven days from the date of blood culture collection was 78% and 50%, respectively. On univariate analysis, the odds ratio of natto intake for B. subtilis bacteremia was 3.6 (95% confidence interval [CI]: 1.2-10.5). Multivariable logistic regression tests after controlling for neutropenia revealed that B. subtilis bacteremia was associated significantly with natto intake at odds ratio 3.3 (95% CI: 1.1-9.6). CONCLUSION: Natto intake was associated with B. subtilis bacteremia during chemotherapy for childhood cancer.

Scallop aquaculture has a potential risk of natto-induced hypersensitivity reactions in a local area of northern Japan.

BACKGROUND: Fermented soybean (natto)-induced hypersensitivity reactions (natto allergy) are rare and can result in late-onset anaphylaxis. The allergen in natto is considered to be poly-γ-glutamic acid (PGA), and marine sports are a risk factor for natto allergy due to epicutaneous sensitization to PGA from cnidarian stings. However, no research on natto allergy in fishery workers has yet been performed. METHODS: We conducted a chart review of inpatients diagnosed with anaphylaxis due to natto at Hokkaido Prefectural Haboro Hospital between April 1, 2009, and August 31, 2020. We also administered self-report questionnaires about food hypersensitivity reactions to Japanese fishery workers, including members of the Kitarumoi Fishery Cooperative Association and part-time workers in this area, from February 1 to May 31, 2021. RESULTS: We found six inpatients (29 inpatients with food-induced anaphylaxis among approximately 11,000 community-dwelling residents) with late-onset anaphylaxis due to natto; all were involved in scallop aquaculture. The questionnaires revealed that 27 participants had natto allergy. We divided the fishery workers into a scallop aquaculture (Scallop) group (n = 211) and other fishery group (n = 106). The Scallop group was significantly associated with natto allergy after adjustments for confounders (OR: 5.73, 95% CI: 1.46-22.56) by logistic regression analysis. In the Scallop group, older age, experience in repairing nets, and a longer length of work experience were significantly related to participants with natto allergy (n = 23), but not participants without natto allergy (n = 181). CONCLUSIONS: Our results indicated an association between scallop aquaculture and natto allergy.

Diagnostic utility of the basophil activation test in natto-induced hypersensitivity.

BACKGROUND: Natto (fermented soybeans)-induced hypersensitivity is characterized by delayed symptom onset that hampers diagnosis. We aimed to clarify the clinical utility of the basophil activation test (BAT) in the diagnosis of natto-induced hypersensitivity. METHODS: Five patients with a history of anaphylaxis and chronic urticaria suspected of natto-induced hypersensitivity and seven with chronic spontaneous urticaria clinically unrelated to natto were enrolled in the patient and control groups, respectively. The BAT was performed with two incubation times, 15 min and 1 h, in combination with various concentrations of natto-mucilage extract. RESULTS: In controls, CD203c levels in basophils remained low in the 15-min incubation but were significantly increased in the 1-h incubation. In the patient group, in the 15-min condition, basophil CD203c was significantly upregulated by natto mucilage but not by soybean vs controls (P = 0.001). Low concentrations of natto mucilage were sufficient to upregulate basophil CD203c in the anaphylaxis cases, but high concentrations were required to induce the same effect in the urticaria cases. Finally, the dose-dependent pattern of the BAT results differed significantly between the anaphylaxis and urticaria cases (P = 0.006). Thus, a strong background reaction was observed in the BAT with 1 h incubation; 15 min of incubation was sufficient to identify patients with natto-induced hypersensitivity and may distinguish the clinical phenotype of natto-induced hypersensitivity, i.e., anaphylaxis or urticaria. CONCLUSIONS: The BAT with a 15-min incubation period is useful in diagnosing natto-induced hypersensitivity.

Behavioral changes and hyperglycemia in NODEF mice following bisphenol S exposure are affected by diets.

Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 µg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 µg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24+CD5+ and %B220+CD40L-cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 µg/kg BW dose groups along with increases in %CD4+CD8+ and %Mac3+CD45R+ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.

Food antigen-specific IgE in dogs with suspected food hypersensitivity.

OBJECTIVE: Knowledge of cross-reactions in food-sensitive dogs will influence the choice of elimination diets and the long-term management of those patients. The objective of this study was to evaluate food allergen-specific IgE tests of suspected allergic dogs for concurrent positive reactions as possible evidence for cross reactions between allergens. MATERIAL AND METHODS: Results of serum IgE tests from 760 suspected allergic dogs submitted to 2 laboratories were evaluated statistically. After the tested allergens were grouped by their phylogenetic relationship, odds ratios as well as a sensitivity analysis of the odds ratios were performed to evaluate if concurrent positive IgE results to 2 allergens occurred more often than expected. RESULTS: Within related allergen pairs 27% (laboratory 1) and 72% (laboratory 2) of the pairs could be considered as associated. For the unrelated allergen pairs only 6.8% and 10.6% of the analyzed pairs were considered associated respectively. Strong correlations were shown in the group of ruminant allergens, especially beef and lamb, and grain allergens. High rates of concurrent reactions were also detected in the poultry group, especially between chicken and duck, as well as between pork and ruminant allergens, and soy and grain allergens. CONCLUSION: As our results showed not only correlations within related but also between non-related allergens, the possible relevance of carbohydrate moieties as well as panallergens for canine hypersensitivities warrants further study. Further investigations are necessary to distinguish co-sensitization from cross-reactions and determine the clinical relevance of food-specific IgE reactivity. CLINICAL RELEVANCE: Due to possible cross reactivity related allergens, especially beef and lamb as well as grain allergens, should not be used for an elimination diet to avoid false results.

Review of the health benefits of habitual consumption of miso soup: focus on the effects on sympathetic nerve activity, blood pressure, and heart rate.

High salt intake increases blood pressure, and dietary salt intake has been clearly demonstrated to be associated with hypertension incidence. Japanese people consume higher amounts of salt than Westerners. It has been reported that miso soup was one of the major sources of daily salt intake in Japanese people. Adding salt is indispensable to make miso, and therefore, in some cases, refraining from miso soup is recommended to reduce dietary salt intake. However, recent studies using salt-sensitive hypertensive models have revealed that miso lessens the effects of salt on blood pressure. In other word, the intake of miso dose not increase the blood pressure compared to the equivalent intake of salt. In addition, many clinical observational studies have demonstrated the absence of a relationship between the frequency of miso soup intake and blood pressure levels or hypertension incidence. The mechanism of this phenomenon seen in the subjects with miso soup intake has not been fully elucidated yet. However, in basic studies, it was found that the ingredients of miso attenuate sympathetic nerve activity, resulting in lowered blood pressure and heart rate. Therefore, this review focused on the differences between the effects of miso intake and those of the equivalent salt intake on sympathetic nerve activity, blood pressure, and heart rate.

Soy Food Intake and Pancreatic Cancer Risk: The Japan Public Health Center-based Prospective Study.

BACKGROUND: Although the poor prognosis and increasing incidence of pancreatic cancer highlight the need for prevention strategies, few lifestyle risk factors for pancreatic cancer have yet been identified. Soybeans contain various bioactive compounds. However, the association between soy food intake and pancreatic cancer risk remains unknown. METHODS: The Japan Public Health Center-based Prospective Study is a cohort study conducted in a general Japanese population. To determine the association of soy food intake and pancreatic cancer incidence, we analyzed 90,185 participants who responded to a questionnaire on medical history and lifestyle factors, including dietary factors based on a food frequency questionnaire in 1995-1998, using Cox proportional hazards models. RESULTS: During a median follow-up of 16.9 years, 577 cases of pancreatic cancer were identified. In the multivariate-adjusted model, total soy food intake was statistically significantly associated with an increased risk of pancreatic cancer [HR for the highest vs. lowest intake quartile: 1.48; 95% confidence interval (CI), 1.15-1.92; P trend = 0.007]. Among soy foods, nonfermented soy food intake showed a statistically significant positive association with pancreatic cancer (HR, 1.41; 95% CI, 1.09-1.81; P trend = 0.008), whereas fermented soy food intake showed no association (HR, 0.96; 95% CI, 0.73-1.26; P trend = 0.982). CONCLUSIONS: Higher intake of soy foods, particularly nonfermented soy foods, might increase pancreatic cancer risk. IMPACT: This study is the first to report an association between the intake of various soy foods and pancreatic cancer risk. Further studies are required to confirm our findings.

Tolerance of soya lecithin in children with non-immunoglobulin E-mediated soya allergy: a randomised, double-blind, cross-over trial.

BACKGROUND: Soya lecithin is present in a wide variety of foods regularly consumed by children, in the form of an emulsifier or stabiliser. Children with non-immunoglobulin (Ig)E-mediated allergies who commonly have to avoid milk and soya will have a significantly restrictive diet with reduced alternative foods if soya lecithin also has to be eliminated. The present study aimed to establish whether children with non-IgE-mediated gastrointestinal soya allergy react to soya lecithin in food products. METHODS: A double-blind, cross-over study was performed in soya-allergic children aged between 8 months and 5 years. Eligible children had their soya allergy status confirmed with a home challenge. Children were randomly assigned to either placebo or challenge dose of soya lecithin (1.5 g per day) in a custom-made biscuit. This was followed by a 1-week washout period and cross-over to another 1 week of challenge or placebo dose. Symptoms were recorded prior to commencing the study and at the end of each week's challenge. RESULTS: Twenty-two children, 16 boys, with a median age of 44 months (range 21-58 months) were recruited, although only 20 completed the full study. The median number of foods avoided in addition to soya was 3. Over the challenge period, the parents reported reactions in six cases: five cases (23%) to the placebo and one case (5%) to the challenge dose. There was no statistical difference (P = 0.025) between the groups. CONCLUSIONS: One child with a non-IgE-mediated gastrointestinal allergy had a slight reaction to soya lecithin. Although single cases may react to soya lecithin, we suggest that soya lecithin should be included in children with this delayed allergy, unless they have a confirmed reaction to traces of soya within this emulsifier.

Effect of transglutaminase cross-linking on the allergenicity of tofu based on a BALB/c mouse model.

Soybean products are limited in terms of safe consumption because of the sensitization of raw materials. In this study, the allergenicity of cross-linked tofu with microbial transglutaminase (MTG) was evaluated on the basis of a BALB/c mouse model. The mice were randomly divided into five groups. Cholera toxin was used as an adjuvant to sensitize the mice through intragastric administration, and tofu was given orally to investigate its sensitization effect on the mice. The allergy symptoms, body temperature, and weight of the mice were detected. The immunoglobulin E (IgE), immunoglobulin G (IgG), and spleen cytokines of the mice were determined through an enzyme-linked immunosorbent assay. The regulation of the differentiation balance of the different subsets of splenic T lymphocyte (Th1, Th2) and regulatory T cells (Tregs) in the mice was measured through flow cytometry. Results showed that the mice administered with MTG-cross-linked tofu had fewer allergic symptoms compared with those of the control group. The concentrations of serum-specific IgE and IgG, plasma histamine, and mast cell protease 1 (mMCP-1) significantly decreased. The Th2-related cytokine levels reduced, and the IFN-γ levels increased. The proportion of Th2 cells decreased, and the proportion of CD4+CD25+Foxp+ Tregs increased as the percentage of Th1 cells increased. Therefore, the sensitization of enzymatic cross-linked tofu decreased.

A Multistate Outbreak of E Coli O157:H7 Infections Linked to Soy Nut Butter.

BACKGROUND: In 2017, we conducted a multistate investigation to determine the source of an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 infections, which occurred primarily in children. METHODS: We defined a case as infection with an outbreak strain of STEC O157:H7 with illness onset between January 1, 2017, and April 30, 2017. Case patients were interviewed to identify common exposures. Traceback and facility investigations were conducted; food samples were tested for STEC. RESULTS: We identified 32 cases from 12 states. Twenty-six (81%) cases occurred in children <18 years old; 8 children developed hemolytic uremic syndrome. Twenty-five (78%) case patients ate the same brand of soy nut butter or attended facilities that served it. We identified 3 illness subclusters, including a child care center where person-to-person transmission may have occurred. Testing isolated an outbreak strain from 11 soy nut butter samples. Investigations identified violations of good manufacturing practices at the soy nut butter manufacturing facility with opportunities for product contamination, although the specific route of contamination was undetermined. CONCLUSIONS: This investigation identified soy nut butter as the source of a multistate outbreak of STEC infections affecting mainly children. The ensuing recall of all soy nut butter products the facility manufactured, totaling >1.2 million lb, likely prevented additional illnesses. Prompt diagnosis of STEC infections and appropriate specimen collection aids in outbreak detection. Child care providers should follow appropriate hygiene practices to prevent secondary spread of enteric illness in child care settings. Firms should manufacture ready-to-eat foods in a manner that minimizes the risk of contamination.

Soy Foods Might Weaken the Sensitivity of Tamoxifen in Premenopausal Patients With Lumina A Subtype of Breast Cancer.

BACKGROUND: Based on estrogen active substances, many women consume soy foods in the belief that it could prevent breast cancer (BC). Women with different molecular subtypes would be likely to have diverse reactions to soy foods, especially those with the estrogen-receptor-positive (ER+) subtype. The aim of the current study is to identify the differentially expressed genes (DEGs) on soy foods in premenopausal patients with Lumina A subtype of BC (LABC) after soy food treatment, and to further investigate the critical molecule change. MATERIALS AND METHODS: GSE58792 retrieved from Gene Expression Omnibus was analyzed to obtain DEGs using GEO2R. Gene Ontology and pathway enrichment analysis were performed using FunRich and GeneMINIA. Overall survival of critical genes was performed by the Kaplan-Meier plotter online tool. RESULTS: A total of 108 DEGs were obtained from the dataset, among which 35 were up-regulated and 73 down-regulated. Soy foods significantly reduced the expression of TFF3, TFF1, GATA3, and ESR1, which were related to the activity of the ER-related pathway and the sensitivity of tamoxifen. Furthermore, the lower expressions of TOX3, FSIP1, ESR1, and CLGN were related to prolonged survival time of patients with BC. The most significant signaling pathways were epithelial-to-mesenchymal transition in up-regulated DEGs, mesenchymal-to-epithelial transition, and mammary gland alveolus development in down-regulated DEGs, which were all related to the development and prognosis of BC. CONCLUSIONS: Soy foods could dramatically alter the ER-related gene profile in LABC. Particularly, down-regulated DEGs of TFF3, TFF1, GATA3, and ESR1 might weaken the sensitivity of tamoxifen and increase the efficacy of neoadjuvant chemotherapy in premenopausal patients with LABC.

Erosive potential of soy-based beverages on dental enamel.

BACKGROUND: This study aimed to investigate the erosive potential of soy-based beverages in comparison to fruit juices of the same flavor. METHODS: Human enamel blocks were randomly divided into 9 groups (n = 8), according to the beverage category (soy or non-soy juices). The initial pH, TA and ß at the original pH value were measured in triplicate. The composition of calcium, phosphate and total protein was analyzed using the specific colorimetric method. The fluoride analysis was performed using a selective electrode. The degree of saturation (DS) and the critical pH (CpH) of each beverage with respect to hydroxyapatite (HAp) and fluorapatite (FAp) were calculated using the computational software. Enamel samples were immersed into 67.5 mL of each drink for 120 minutes. Enamel surface loss (ESL) and differences in surface roughness (ΔRaE-S) were analyzed by a 3D non-contact profilometer. RESULTS: Non-soy beverages exhibited the lowest pH values (2.93 to 3.40). The highest values of calcium concentration were founded in soy-based formulations. Juices with soy in their composition tend to have high DS when compared with non-soy based beverages (p = .0571). Soy beverages produced less ESL than non-soy beverages (p < .05). ΔRaE-S was not significantly different between the categories. The ESL and ΔRaE-S were positively correlated with initial pH and buffering capacity in soy-based beverages. On the other hand, in non-soy beverages, the ESL was negatively correlated with the TA to 7.0 and the fluoride composition whereas the ΔRaE-S was negatively correlated with the TA to 5.5. CONCLUSIONS: The erosive potential of soy beverages was lower than non-soy based beverages.

Isotretinoin in severe peanut- and soy-allergic patients: is it safe or not?

No disponible

Acute effect of soy and soy products on serum uric acid concentration among healthy Chinese men.

BACKGROUND AND OBJECTIVES: Soy products are essential to the daily life of the Chinese population. However, the association between soy products and serum uric acid remains unclear. Better understanding of their relationship could provide food choice information for patients with gout. This study assessed the acute effects of soy and soy products on serum uric acid. METHODS AND STUDY DESIGN: Sixty healthy adult male volunteers were recruited and randomly assigned to six groups. Ten participants in each group randomly ingested one of six foods: water, soy, and four different soy products. A blood test was conducted after 3 h to examine uric acid concentration. RESULTS: The serum uric acid concentration significantly increased by 21.4±23.4 µmol/L at 1 h and 16.3±19.4 µmol/L at 2 h following ingestion of whole soybeans. These changes also applied to the soy powder group. The serum uric acid concentration rapidly increased by 38.1±20.5 µmol/L at 1 h, 34.4±18.2 µmol/L at 2 h, and 24.1±24.2 µmol/L at 3 h after the ingestion of soybean milk. The maximum concentration of serum uric acid was observed at 1 h after intake of soybeans and soy products, and then gradually decreased during the subsequent 2-h period. No significant uric acid changes from ingesting bean curd cake and dried bean curd stick were detected. CONCLUSIONS: Ingesting different soy products resulted in different concentrations of serum uric acid, with soybeans, soybean milk, and soy powder considerably increasing serum uric acid.

Soy product and isoflavone intake associations with allergic diseases in Japanese workers: rhinitis, dermatitis and asthma.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the associations of intake of soy products and isoflavones with allergic diseases. METHODS AND STUDY DESIGN: We conducted a cross-sectional study in 1437 participants (aged 20-64 years) who were living in Tokushima Prefecture, Japan during the period 2010- 2011. We obtained anthropometric data and information on life style characteristics including dietary intake and current medical histories of allergic diseases using a structural self-administered questionnaire. Multiple logistic regression models were used to assess the associations of soy products and isoflavones with allergic diseases after controlling for age, family history of allergic diseases, smoking, drinking, physical activity, energy intake, BMI and dietary factors. RESULTS: Intake of soy products showed significant inverse dose-response relationships with allergic rhinitis. The third quartile for soy products had an adjusted OR of 0.56 (95% CI: 0.35-0.91) compared to the reference group (first quartile), though intake of soy products showed no dose-response relationship with atopic dermatitis. Intake of soy isoflavones showed a significant inverse dose-response relationship with atopic dermatitis, though the association between intake of soy isoflavones and atopic dermatitis was U-shaped after adjustments for potential confounders. On the other hand, the associations between intake of soy isoflavones and other allergic diseases were not significant. CONCLUSIONS: The results indicate that higher intake of soy products is associated with reduced risk of allergic rhinitis in Japanese workers. Furthermore, moderate intake amounts of soy products and soy isoflavones are associated with inverse risk of atopic dermatitis.

Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review.

BACKGROUND AND OBJECTIVES: To evaluate the associations of dietary factors and the risk of gout and hyperuricemia. METHODS AND STUDY DESIGN: PubMed and Embase databases were searched from inception to June 2017 for eligible studies. Nineteen prospective cohort or cross-sectional studies with adequate sample sizes are included, all involving red meat, seafoods, alcohol, fructose, dairy products, soy foods, high-purine vegetables and coffee. RESULTS: Meta-analysis revealed several dietary associations with gout risk: red meat: OR 1.29 (95% CI 1.16-1.44); seafoods: OR 1.31 (95% CI 1.01-1.68); alcohol: OR 2.58 (95% CI 1.81-3.66); fructose: OR 2.14 (95% CI 1.65- 2.78); dairy products: OR 0.56 (95% CI 0.44-0.70); soy foods: OR 0.85 (95% CI 0.76-0.96); high-purine vegetables: OR 0.86 (95% CI 0.75-0.98); coffee: OR 0.47 (95% CI 0.37-0.59).Dietary association with hyperuricemia risk (red meat: OR 1.24 (95% CI 1.04-1.48); seafoods: OR 1.47 (95% CI 1.16-1.86); alcohol: OR 2.06 (95% CI 1.60-2.67); fructose: OR 1.85 (95% CI 1.66-2.07); dairy products: OR 0.50 (95% CI 0.37-0.66); soy foods: OR 0.70 (95% CI 0.56-0.88); high-purine vegetables ingestion: OR 1.10 (95% CI 0.88-1.39), P=0.39; coffee:OR0.76 in men (95% CI 0.55-1.06), OR 1.58 in women (95% CI 1.16-2.16). CONCLUSION: The risk of hyperuricemia and gout is positively correlated with the intake of red meat, seafoods, alcohol or fructose, and negatively with dairy products or soy foods. High-purine vegetables showed no association with hyperuricemia, but negative association with gout. Coffee intake is negatively associated with gout risk, whereas it may be associated with increased hyperuricemia risk in women but decreased risk in men.

Frequent milk and soybean consumption are high risks for uterine leiomyoma: A prospective cohort study.

This study aims to retrospectively analyze the potential risk factors for uterine leiomyoma and prospectively examine whether these risk factors can increase the incidence of uterine leiomyoma.Women who attended our outpatient department from January 1, 2010 to December 31, 2010 were enrolled. General demographical characteristics, personal information, and living habits were collected. Univariate and multivariate logistic regression analyses were used to identify the potential risk factors. Follow-up was regularly conducted to complete the prospective analysis.A total of 1273 women were enrolled including 213 uterine leiomyomas (case group) and 1060 nonuterine leiomyoma women (control group). No statistical differences were found on the age, marital status, number and complication of pregnancy, frequent physical exercise, frequent alcohol consumption, and family history of uterine diseases between two groups (all P > .05). Mean body mass index (P = .043), high school education (P = .041), frequent smoking (P = .030), frequent caffeine consumption (P = .019), frequent milk or soybean consumption (P = .025), and frequent oral contraceptive use (P = .034) were statistically correlated with the onset of uterine leiomyoma. Multivariate analysis verified that frequent milk or soybean consumption (7.349 [5.081-9.454]; P = .039] and frequent oral contraceptive use (8.103 [4.486-12.583]; P = .018] were the independent risk factors for uterine leiomyoma.Frequent milk or soybean consumption and frequent oral contraceptive use are associated with a high risk of uterine leiomyoma, and proper education on the prevention of uterine leiomyoma is highly recommended in clinical practice.